Diisopropylethylamine → ethyl 4-(5-chloropyrazin-2-yl)-2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl]-1,3-thiazole-5-carboxylate

HRID 655738Notes

Reaction equation

HRID 655738 reaction equation
[Cl:1][C:2]1[C:6]([Cl:7])=[C:5]([CH3:8])[NH:4][C:3]=1[C:9]([NH:11][C@@H:12]1[CH2:17][CH2:16][NH:15][CH2:14][C@@H:13]1[O:18][CH2:19][CH3:20])=[O:10].Br[C:22]1[S:23][C:24]([C:34]([O:36][CH2:37][CH3:38])=[O:35])=[C:25]([C:27]2[CH:32]=[N:31][C:30]([Cl:33])=[CH:29][N:28]=2)[N:26]=1.C(N(CC)C(C)C)(C)C>CN1CCCC1>[Cl:33][C:30]1[N:31]=[CH:32][C:27]([C:25]2[N:26]=[C:22]([N:15]3[CH2:16][CH2:17][C@@H:12]([NH:11][C:9]([C:3]4[NH:4][C:5]([CH3:8])=[C:6]([Cl:7])[C:2]=4[Cl:1])=[O:10])[C@@H:13]([O:18][CH2:19][CH3:20])[CH2:14]3)[S:23][C:24]=2[C:34]([O:36][CH2:37][CH3:38])=[O:35])=[N:28][CH:29]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 58074997Ethyl 2-bromo-4-(5-chloropyrazin-2-yl)-1,3-thiazole-5-carboxylate2×HCID 594025453,4-dichloro-N-[(3S,4R)-3-ethoxypiperidin-4-yl]-5-methyl-1H-pyrrole-2-carboxamide2×

Product 1

HCID 59402522ethyl 4-(5-chloropyrazin-2-yl)-2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl]-1,3-thiazole-5-carboxylateYield 88.4%

Reagents, catalysts & solvents 1

HCID 84541-MethylpyrrolidineSolvent

Procedure

To the stirred the solution of 3,4-dichloro-N-[(3S,4R)-3-ethoxypiperidin-4-yl]-5-methyl-1H-pyrrole-2-carboxamide (Intermediate 26, 650 mg, 2.03 mmol) and ethyl 2-bromo-4-(5-chloropyrazin-2-yl)-1,3-thiazole-5-carboxylate (Intermediate 47, 636 mg, 1.828 mmol) in N-methylpyrrolidine was added N,N-diisopropyl ethylamine and stirred at stirred at 60° C. for 3 h. The reaction mixture was cooled to room temperature and poured on to ice water. The precipitate was collected by filtration and dried to afford 950 mg (79%) of ethyl 4-(5-chloropyrazin-2-yl)-2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl]-1,3-thiazole-5-carboxylate.

Workup

  1. stirringat stirred at 60° C. for 3 h
  2. filtrationThe precipitate was collected by filtration
  3. customdried

Sources & evidence

ORD record
ord-2f6e2df26d374d888dfb7b9784c882ed
Source dataset
uspto-grants-2011_12
Patent number
US08071605B2

Reaction notes

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