Diisopropylethylamine → HCID 25206449, compound

HRID 387654Notes

Reaction equation

HRID 387654 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.[CH3:30][N:31]([S:53]([CH3:56])(=[O:55])=[O:54])[C:32]1[CH:33]=[C:34]([C:50](O)=[O:51])[C:35]2[CH2:36][CH2:37][N:38]([CH:43]([CH2:47][CH2:48][CH3:49])[CH2:44][CH2:45][CH3:46])[C:39](=[O:42])[C:40]=2[CH:41]=1.OC1C2N=NNC=2C=CC=1.Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C>ClCCl.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:50]([C:34]1[C:35]2[CH2:36][CH2:37][N:38]([CH:43]([CH2:47][CH2:48][CH3:49])[CH2:44][CH2:45][CH3:46])[C:39](=[O:42])[C:40]=2[CH:41]=[C:32]([N:31]([CH3:30])[S:53]([CH3:56])(=[O:55])=[O:54])[CH:33]=1)=[O:51])[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

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 68469685HCID 68469685, compoundHCID 86643873HCID 86643873, compoundHCID 178418300HCID 178418300, compound

Product 1

HCID 25206449HCID 25206449, compoundYield 79.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Poured into a suspension of 233 mg of (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-({1-[3-(trifluoromethyl)phenyl]cyclopropyl}amino)butan-2-ol hydrochloride (2:1), 278 mg of 7-[methyl(methylsulfonyl)amino]-1-oxo-2-(1-propylbutyl)-1,2,3,4-tetrahydroisoquinoline-5-carboxylic acid, 12 mg of hydroxybenzotriazole and 142 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride in 10 cm3 of dichloromethane is 0.4 cm3 of N,N-diisopropylethylamine at a temperature close to 20° C. The solution is kept stirring for 20 h at a temperature close to 20° C. 20 cm3 of water are added to the reaction medium. After decanting, the organic phase is filtered through a pellet of 15 g of 40-63 μm silica. The silica pellet is washed firstly with 150 cm3 of dichloromethane then secondly with 150 cm3 of a mixture of 50% ethyl acetate/50% dichloromethane. This second filtrate is concentrated using a rotary evaporator under reduced pressure (5 kPa). 330 mg of N-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({1-[3-(trifluoromethyl)phenyl]cyclopropyl}amino)propyl]-7-[methyl(methylsulfonyl)amino]-1-oxo-2-(1-propylbutyl)-1,2,3,4-tetrahydroisoquinoline-5-carboxamide are obtained in the form of a white foam.

Workup

  1. customclose to 20° C
  2. customclose to 20° C
  3. customAfter decanting
  4. filtrationthe organic phase is filtered through a pellet of 15 g of 40-63 μm silica
  5. washThe silica pellet is washed firstly with 150 cm3 of dichloromethane
  6. concentrationThis second filtrate is concentrated
  7. customa rotary evaporator under reduced pressure (5 kPa)

Sources & evidence

ORD record
ord-b10b036c503c4169b2b9c62b62b15e2d
Source dataset
uspto-grants-2013_02
Patent number
US08372864B2

Reaction notes

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