Ammonia → HCID 71539494, compound

HRID 1915872Notes

Reaction equation

HRID 1915872 reaction equation
C(OC([NH:8][C:9]1[S:13][C:12]([C:14]2[C:19]([F:20])=[CH:18][CH:17]=[CH:16][C:15]=2[F:21])=[N:11][C:10]=1[C:22]([NH:24][C:25]1[CH:26]=[N:27][N:28]([CH3:45])[C:29]=1[N:30]1[CH2:35][C@H:34]([F:36])[CH2:33][C@@H:32]([NH:37]C(=O)OC(C)(C)C)[CH2:31]1)=[O:23])=O)(C)(C)C.N>Cl.CO.CO>[NH2:8][C:9]1[S:13][C:12]([C:14]2[C:15]([F:21])=[CH:16][CH:17]=[CH:18][C:19]=2[F:20])=[N:11][C:10]=1[C:22]([NH:24][C:25]1[CH:26]=[N:27][N:28]([CH3:45])[C:29]=1[N:30]1[CH2:35][C@H:34]([F:36])[CH2:33][C@@H:32]([NH2:37])[CH2:31]1)=[O:23]

Participants

5

Reactant 2

HCID 222AmmoniaHCID 86680077HCID 86680077, compound

Product 1

HCID 71539494HCID 71539494, compoundYield 74.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 21893726Hydrochloride methanolSolvent

Procedure

A mixture of tert-butyl (3R,5R)-1-(4-(5-(tert-butoxycarbonylamino)-2-(2,6-difluorophenyl)-thiazole-4-carboxamido)-1-methyl-1H-pyrazol-5-yl)-5-fluoropiperidin-3-ylcarbamate (150 mg, 0.23 mmol) in HCl/MeOH (10 mL) was stirred at ambient temperature for 20 hours and concentrated under reduced pressure to afford a residue. The residue was diluted with MeOH (10 mL), neutralized with 28% ammonia solution, and concentrated to give a crude product. The crude product was purified by preparative HPLC to give 159 as pale solid (77 mg, 74%). 1H NMR (500 MHz, CD3OD) δ (ppm): 7.74 (s, 1H), 7.48-7.42 (m, 1H), 7.14-7.11 (m, 2H), 5.36-5.24 (m, 1H), 4.00-3.94 (m, 1H), 3.83-3.72 (m, 4H), 3.42-3.37 (m, 1H), 2.74-2.62 (m, 2H), 2.50-5.42 (m, 1H), 2.02-1.88 (m, 1H); MS (ESI) m/z: 452 [M+H+].

Workup

  1. concentrationconcentrated under reduced pressure
  2. customto afford a residue
  3. concentrationconcentrated
  4. customto give a crude product
  5. customThe crude product was purified by preparative HPLC

Sources & evidence

ORD record
ord-858ead5302104bd0b59a14e47f244d8c
Source dataset
uspto-grants-2013_12
Patent number
US08614206B2

Reaction notes

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