Diisopropylethylamine → HCID 25206131, compound

HRID 387639Notes

Reaction equation

HRID 387639 reaction equation
Cl.[NH2:2][C@@H:3]([CH2:21][C:22]1[CH:27]=[C:26]([F:28])[CH:25]=[C:24]([F:29])[CH:23]=1)[C@H:4]([OH:20])[CH2:5][NH:6][C:7]1([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([F:19])([F:18])[F:17])[CH:11]=2)[CH2:9][CH2:8]1.[O:30]=[C:31]1[C:40]2[CH:39]=[CH:38][CH:37]=[C:36]([C:41](O)=[O:42])[C:35]=2[CH2:34][CH2:33][N:32]1[CH2:44][CH2:45][CH2:46][CH2:47][CH3:48].OC1C2N=NNC=2C=CC=1.Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C>ClCCl.C(OCC)C.O>[F:29][C:24]1[CH:23]=[C:22]([CH:27]=[C:26]([F:28])[CH:25]=1)[CH2:21][C@H:3]([NH:2][C:41]([C:36]1[C:35]2[CH2:34][CH2:33][N:32]([CH2:44][CH2:45][CH2:46][CH2:47][CH3:48])[C:31](=[O:30])[C:40]=2[CH:39]=[CH:38][CH:37]=1)=[O:42])[C@H:4]([OH:20])[CH2:5][NH:6][C:7]1([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([F:17])([F:18])[F:19])[CH:11]=2)[CH2:9][CH2:8]1

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 68469137HCID 68469137, compoundHCID 86643873HCID 86643873, compoundHCID 178418300HCID 178418300, compound

Product 1

HCID 25206131HCID 25206131, compoundYield 81.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent2×

Procedure

326 mg of (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-({1-[3-(trifluoromethyl)phenyl]cyclopropyl}amino)butan-2-ol hydrochloride (2:1), 180 mg of 1-oxo-2-pentyl-1,2,3,4-tetrahydroisoquinoline-5-carboxylic acid, 14 mg of hydroxybenzotriazole, 165 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 0.47 cm3 of N,N-diisopropylethylamine in 18 cm3 of dichloromethane are stirred for 20 h at a temperature close to 20° C. 10 cm3 of water and dichloromethane are added to the reaction medium. The suspension is filtered, washed successively with water and dichloromethane. The solid obtained is taken up in ethyl ether, filtered, washed with ethyl ether and dried under vacuum at 20° C. 360 mg of N-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({1-[3-(trifluoromethyl)phenyl]cyclopropyl}amino)propyl]-1-oxo-2-pentyl-1,2,3,4-tetrahydroisoquinoline-5-carboxamide are obtained in the form of a white solid.

Workup

  1. customclose to 20° C
  2. filtrationThe suspension is filtered
  3. washwashed successively with water and dichloromethane
  4. customThe solid obtained
  5. filtrationfiltered
  6. washwashed with ethyl ether
  7. customdried under vacuum at 20° C

Sources & evidence

ORD record
ord-5cf512d38e904e35a981dbc59998b077
Source dataset
uspto-grants-2013_02
Patent number
US08372864B2

Reaction notes

Loading…