Diisopropylethylamine → HCID 25206293, compound

HRID 387634Notes

Reaction equation

HRID 387634 reaction equation
[CH2:1]([N:8]1[CH2:17][CH2:16][C:15]2[C:14]([C:18]([OH:20])=O)=[CH:13][CH:12]=[CH:11][C:10]=2[C:9]1=[O:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[NH2:23][C@@H:24]([CH2:42][C:43]1[CH:48]=[C:47]([F:49])[CH:46]=[C:45]([F:50])[CH:44]=1)[C@H:25]([OH:41])[CH2:26][NH:27][C:28]1([C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([C:37]([F:40])([F:39])[F:38])[CH:32]=2)[CH2:30][CH2:29]1.Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C>ClCCl.OC1C2N=NNC=2C=CC=1>[CH2:1]([N:8]1[CH2:17][CH2:16][C:15]2[C:14]([C:18]([NH:23][C@@H:24]([CH2:42][C:43]3[CH:44]=[C:45]([F:50])[CH:46]=[C:47]([F:49])[CH:48]=3)[C@H:25]([OH:41])[CH2:26][NH:27][C:28]3([C:31]4[CH:36]=[CH:35][CH:34]=[C:33]([C:37]([F:38])([F:39])[F:40])[CH:32]=4)[CH2:30][CH2:29]3)=[O:20])=[CH:13][CH:12]=[CH:11][C:10]=2[C:9]1=[O:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 684716621,2,3,4-Tetrahydro-1-oxo-2-(phenylmethyl)-5-isoquinolinecarboxylic acidHCID 86643873HCID 86643873, compound

Product 1

HCID 25206293HCID 25206293, compoundYield 169.5%

Reagents, catalysts & solvents 2

HCID 178418300HCID 178418300, compoundCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A solution of 100 mg of 2-benzyl-1-oxo-1,2,3,4-tetrahydroisoquinoline-5-carboxylic acid, 168 mg of (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-({1-[3-(trifluoromethyl)phenyl]cyclopropyl}amino)butan-2-ol hydrochloride (2:1), 7.2 mg of hydroxybenzotriazole, 85 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 0.243 cm3 of N,N-diisopropylethylamine in 10 cm3 of dichloromethane is stirred at a temperature close to 20° C. for 20 h. Dichloromethane is added to the reaction medium. The organic phase is washed with water then with a saturated aqueous solution of sodium chloride, dried over sodium sulfate and concentrated using a rotary evaporator under reduced pressure (5 kPa). The 400 mg of product obtained are purified by flash chromatography over silica (column: 50 g; particle size: 15-40 μm; eluent: 100% ethyl acetate). After concentrating the fractions under reduced pressure, 103 mg of 2-benzyl-N-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({1-[3-(trifluoromethyl)phenyl]cyclopropyl}amino)propyl]-1-oxo-1,2,3,4-tetrahydroisoquinoline-5-carboxamide are obtained.

Workup

  1. customclose to 20° C. for 20 h
  2. washThe organic phase is washed with water
  3. dry with materialwith a saturated aqueous solution of sodium chloride, dried over sodium sulfate
  4. concentrationconcentrated
  5. customa rotary evaporator under reduced pressure (5 kPa)

Sources & evidence

ORD record
ord-deddc92244fb4251906a9aea16eedc76
Source dataset
uspto-grants-2013_02
Patent number
US08372864B2

Reaction notes

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