Hydrochloric Acid → 5-Amino-2-(2,6-difluorophenyl)-N-(5-(3,3-difluoropiperidin-1-yl)-1-methyl-1H-pyrazol-4-yl)thiazole-4-carboxamide

HRID 2089402Notes

Reaction equation

HRID 2089402 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[S:10][C:11]([NH:31]C(=O)OC(C)(C)C)=[C:12]([C:14](=[O:30])[NH:15][C:16]2[CH:17]=[N:18][N:19]([CH3:29])[C:20]=2[N:21]2[CH2:26][CH2:25][CH2:24][C:23]([F:28])([F:27])[CH2:22]2)[N:13]=1.Cl>CO.O1CCOCC1>[NH2:31][C:11]1[S:10][C:9]([C:3]2[C:2]([F:1])=[CH:7][CH:6]=[CH:5][C:4]=2[F:8])=[N:13][C:12]=1[C:14]([NH:15][C:16]1[CH:17]=[N:18][N:19]([CH3:29])[C:20]=1[N:21]1[CH2:26][CH2:25][CH2:24][C:23]([F:27])([F:28])[CH2:22]1)=[O:30]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 67437761tert-butyl 2-(2,6-difluorophenyl)-4-(5-(3,3-difluoropiperidin-1-yl)-1-methyl-1H-pyrazol-4-ylcarbamoyl)thiazol-5-ylcarbamate

Product 1

HCID 584649185-Amino-2-(2,6-difluorophenyl)-N-(5-(3,3-difluoropiperidin-1-yl)-1-methyl-1H-pyrazol-4-yl)thiazole-4-carboxamideYield 63.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of tert-butyl 2-(2,6-difluorophenyl)-4-(5-(3,3-difluoropiperidin-1-yl)-1-methyl-1H-pyrazol-4-ylcarbamoyl)thiazol-5-ylcarbamate (57 mg, 0.1 mmol) in MeOH (2 mL) was added HCl in 1,4-dioxane (4 M, 5 mL). After stirring at room temperature for 18 hr the mixture was concentrated under reduced pressure. Purification via preparative HPLC gave 287 as a white solid (29 mg, 63%). 1H NMR (400 MHz, CDCl3) δ 8.40 (s, 1H), 7.65 (s, 1H), 7.37-7.28 (m, 1H), 7.06-6.99 (m, 2H), 6.13 (s, 2H), 3.75 (s, 3H), 3.32 (t, J=11.0 Hz, 2H), 3.17-3.12 (m, 2H), 2.08-1.95 (m, 2H), 1.92-1.84 (m, 2H). LCMS (ES+) m/z 455.0 (M+1).

Workup

  1. concentrationwas concentrated under reduced pressure
  2. customPurification via preparative HPLC

Sources & evidence

ORD record
ord-cd694c4fe3fa4203ae573a5aa905d82f
Source dataset
uspto-grants-2013_05
Patent number
US08436001B2

Reaction notes

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