509
May 1967 TABLEI AMIDESOF 0-ETHOXYBENZOIC ACID
q c o R OC?Hj M p or h p i m m ) , OC
R
So.
Yield purified,
YQ
Purification sollenta
-Carbon, Calcd
Formula
-Hydrogen, %Calcd round
%round
-Nitrogen, %Calcd Found
SH-3-CjH4Kh 66-68 33 A C14H14N?O? 69.40 69.84 5.82 6.12 11.57 74.58 6.27 6.29 5.81 NI-TCsHj 70-71 50 A C1OH1&0> 74.66 7.5.73 7.11 7.28 5.20 CiiHisXOs 75.81 112-114 ( 0 . 2 ) 49 , . N(C2Hj)GHj 76.09 7.11 7.25 5.20 4 NH(CH~)?CGH: 5648 28 A CliH1&O? 75.81 71.60 7.07 6.69 4.92 CliHi9N03 71.59 54-56 50 B 5 NHCH~C~H~-~-CHIO 76.33 7.47 7.48 4.94 6 Y(CsHj)cH,c6H: 133-135 (0.1) 33 .. CisHziNO? 76.29 79.79 6.03 6.09 4.42 7 N(CGHO)~ 97-99 78 A C?1HiS?jO? 79.47 76.46 9.49 9.54 4.25 8 N(CGHII)~' 170-172 (0.3) 32 . . CsiH3iNOa 76.55 a A, isooctane; B, ethanol-water. C:,HaN represent's t'he pyridyl radical. C6Hl1 represents the cvclohesyl radical. 1 2 3
11.60 5.46 .5.1.5
5.09 4.80 4.01 4.49 4.17
TABLE 11 AMIDESO F p-ISOPROPYLBEXZOIC A4CID
No.
9
10 11 12 13 14 15 16 17 18 a-c
R
.\Ip or bp (mm), ' C
Yield Purifipuri- cation fie& sol70 venta
.. 97-100 (0.4) 25 S(CtH&)?d 14 A 100-101 XH-3-CjH4N" 37 A 60-61 X(CHz)5 43 B 129-131 NHC6Hj 38 A 80-81 N(CH,)(CsH1l)c 124-127(0.2) 36 .. S(C?Hj)(CeHj) 19 B Y H ( C H ~ ) ~ C ~ H S 110-1 12 33 B ?;HCHzCGHe-p-~IeO 119-12 1 .. 168-169 ( 0 . 4 ) 12 N(C2Hz)CHsCsHj 170-172 (0.1) 43 .. N(CGH~~)~ W. F. Barth See rorresponding footncites, Table I.
--Carbon, Calcd
76.41 9.65 9.72 76.66 6.38 75.12 74.97 6.71 6.77 11.66 77.87 9.15 77.89 9.36 6.06 80.04 7.16 80.30 7.19 5.85 78.98 9.72 78.71 5.40 9.95 80.64 7.92 7.87 80.86 5.24 80.59 7.92 7.90 80.86 j.24 76.08 7.47 7.43 76.29 4.94 81.10 80.99 8.24 8.49 4.98 80.19 9.60 81.18 9.68 4.30 d S.A . Hall, J . Org. Chem., 19, 485 (1954).
ANTIXXLARL~L TESTI)ATA
Acknowledgment.-The authors wish to t,hank 1Tr. Charles E. Childs and his staff for the microanalytiral data reported herein. Compd
PETERK. IBERASD BETTYJ. BOOXE Division of Biochemistry, FValter Reed A r m y Institute of Research, Washington, D . C. 20012
Received September 29, 1966 Renised Manuscript Receiued Januaru 19, 1967 Increased interest in finding a prophylactic agent against dnigresistant Plasmodium j a l c i p a m m and Plaswaodium viuax has led to the synthesis of two new substituted qliinolines, 4-(1-methyl-4pyrrolidinobuty1amino)-7-chloroquinoline (I) and 4-(l-methyl4-morpholinobutylamino)-i-chloroquinoline(11)(Table I ) . 4-(1~~ethyl-4-bromobutylamino)-i-chl~~roq~iiriolirie (III),l upon reaction with morpholine or pyrrolidine, gave I and 11, respectively. Preliminary reports2 show these compounds to be artive against Plasmodium berghei infected mice. (1) M. Carmack, H. Rullitt, J r . , G. Handrick, L. W. Kisainger, and I. Von, .I. A m . Clwm. Soc., 68, 1220 (1946).
6.21 11.47 6.12 5.96 5.35 5.17 -5.26 4.82 4.81 4.19
TABLEI
from the original filtrate was removed in zmxo and the residiie wns recrystallized or distilled.
4-(l-Meth~l-4-pyrrolidinobutylamino)-7chloroquinoline and 4-(l-Methyl-4-morpholinobutylamino)-7-chloroquinolineas Potential Antimalarials
--Nitrogen, 47Calrd 1:oiind
-Hydrogen, %Calcd Found
% ;' Foiind
I I1 I1
No. of mice"
Dose, mg/kg
Mean survival time, days*
Deaths
40 15.2 5 3 80 13.8 4 3 160 14.4 4 a Mice iriferted with P . berghei. Treatment is withheld for 3 days after infection. Death orciirs in iintreated control.: within 6-8 days. J
c1 NH
I
CH,~(CH~J,R I, R = pyrrolidino 11, R = morpholino Experimental Section3
4 4 1-Methyl-4-pyrrolidinobutylamino)-7-chloroquino~ine (I).4-(l-~\lethyl-4-bromoblltylamino)-i-chloroqiiinoline (111)' (13.2 ( 2 ) We wish t o thank Dr. Leo Rane, University of Miami, Miami, Fla., for t h e preliminary test data. (3) Melting points are uncorrected and were determined on a FisherJohns melting point apparatus. T h e microanalyses were berformed by hIr. Joseph hlicino, Metuchen, N. J. 08840.
