Diisopropylethylamine → (S)-tert-butyl (2-(4-(3-amino-6-(4,4-difluorocyclohexyl)pyrazin-2-yl)-2-fluorobenzamido)-2-(3-chlorophenyl)ethyl)carbamate

HRID 596052Notes

Reaction equation

HRID 596052 reaction equation
[NH2:1][C:2]1[C:3]([C:16]2[CH:24]=[CH:23][C:19]([C:20](O)=[O:21])=[C:18]([F:25])[CH:17]=2)=[N:4][C:5]([CH:8]2[CH2:13][CH2:12][C:11]([F:15])([F:14])[CH2:10][CH2:9]2)=[CH:6][N:7]=1.CCN(C(C)C)C(C)C.[NH2:35][C@@H:36]([C:46]1[CH:51]=[CH:50][CH:49]=[C:48]([Cl:52])[CH:47]=1)[CH2:37][NH:38][C:39](=[O:45])[O:40][C:41]([CH3:44])([CH3:43])[CH3:42].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CS(C)=O>[NH2:1][C:2]1[C:3]([C:16]2[CH:24]=[CH:23][C:19]([C:20]([NH:35][C@@H:36]([C:46]3[CH:51]=[CH:50][CH:49]=[C:48]([Cl:52])[CH:47]=3)[CH2:37][NH:38][C:39](=[O:45])[O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:21])=[C:18]([F:25])[CH:17]=2)=[N:4][C:5]([CH:8]2[CH2:9][CH2:10][C:11]([F:14])([F:15])[CH2:12][CH2:13]2)=[CH:6][N:7]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 69108925[(S)-2-amino-2-(3-chloro-phenyl)-ethyl]-carbamic acid tert-butyl esterHCID 1180456884-(3-Amino-6-(4,4-difluorocyclohexyl)pyrazin-2-yl)-2-fluorobenzoic acid

Product 1

HCID 118054654(S)-tert-butyl (2-(4-(3-amino-6-(4,4-difluorocyclohexyl)pyrazin-2-yl)-2-fluorobenzamido)-2-(3-chlorophenyl)ethyl)carbamateYield 14.7%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

To 4-(3-amino-6-(4,4-difluorocyclohexyl)pyrazin-2-yl)-2-fluorobenzoic acid (48 mg, 0.124 mmol) were added DMSO (1 mL), Hünig's base (0.108 mL, 0.619 mmol), (S)-tert-butyl (2-amino-2-(3-chlorophenyl)ethyl)carbamate (50.3 mg, 0.186 mmol) and then HATU (94 mg, 0.248 mmol). The reaction was stirred for 1 h at room temperature. To the reaction was added 0.5 mL of DMSO, filtered, purified by prep HPLC, and lyophilized to give 11 mg of the desired product used as is (12% yield). LCMS (m/z): 604.2 (MH+), 1.05 min.

Workup

  1. filtrationfiltered
  2. custompurified by prep HPLC

Sources & evidence

ORD record
ord-1d019b58cf134778af6b1b6bcce24cf1
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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