Ammonia → HCID 73603017, compound

HRID 1915886Notes

Reaction equation

HRID 1915886 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 86680091HCID 86680091, compound

Product 1

HCID 73603017HCID 73603017, compoundYield 90%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 21893726Hydrochloride methanolSolvent

Procedure

A mixture of tert-butyl (3S,5S)-1-(4-(5-(tert-butoxycarbonylamino)-2-(2,6-difluorophenyl)thiazole-4-carboxamido)-1-methyl-1H-pyrazol-5-yl)-5-fluoropiperidin-3-ylcarbamate (208 mg, 0.32 mmol) in HCl/MeOH (10 mL) was stirred at ambient temperature for 20 hours and concentrated reduced pressure to give 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 afford 189 (130 mg, 90%) as solid. 1H NMR (500 MHz, DMSO) δ (ppm): 8.82 (s, 1H), 7.56-7.51 (m, 3H), 7.41 (s, 1H), 7.30-7.26 (m, 2H), 4.80-4.65 (m, 1H), 3.64 (s, 3H), 3.06-2.98 (m, 2H), 2.89-2.84 (m, 1H), 2.70-2.66 (m, 1H), 2.23-2.18 (m, 1H), 1.72 (br s, 3H), 1.41-1.32 (m, 1H); MS (ESI) m/z: 452 [M+H+].

Workup

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

Sources & evidence

ORD record
ord-46aea640a17442848a014da66a60bed4
Source dataset
uspto-grants-2013_12
Patent number
US08614206B2

Reaction notes

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