Diethyl Ether → tert-Butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)piperidine-1-carboxylate

HRID 1779105Notes

Reaction equation

HRID 1779105 reaction equation
C(OCC)C.Cl[C:7]1[N:12]=[C:11]([Cl:13])[C:10]([C:14]([F:17])([F:16])[F:15])=[CH:9][N:8]=1.[NH2:18][C:19]1[CH:20]=[N:21][N:22]([CH:24]2[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH2:25]2)[CH:23]=1.CCN(CC)CC>CC(O)(C)C.ClCCCl.[Cl-].[Cl-].[Zn+2]>[Cl:13][C:11]1[C:10]([C:14]([F:17])([F:16])[F:15])=[CH:9][N:8]=[C:7]([NH:18][C:19]2[CH:20]=[N:21][N:22]([CH:24]3[CH2:25][CH2:26][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:28][CH2:29]3)[CH:23]=2)[N:12]=1

Participants

8

Reactant 4

HCID 3283Diethyl EtherHCID 8471TriethylamineHCID 27827742,4-Dichloro-5-(trifluoromethyl)pyrimidineHCID 27281520tert-butyl 4-(4-amino-1H-pyrazol-1-yl)piperidine-1-carboxylate

Product 1

HCID 86712281tert-Butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)piperidine-1-carboxylateYield 71%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 111,2-DichloroethaneSolvent2×HCID 6386tert-ButanolSolvent2×

Procedure

A 1.0 M solution of ZnCl2 in diethyl ether (20.7 mL, 20.7 mmol) was added to a solution of 2,4-dichloro-5-(trifluoromethyl)pyrimidine (4.48 g, 20.7 mmol) in t-BuOH (100 mL) and DCE (100 mL). The mixture was stirred for 10 minutes then diluted with t-BuOH (100 mL) and DCE (100 mL) before tert-butyl 4-(4-amino-1H-pyrazol-1-yl)piperidine-1-carboxylate (5.00 g, 18.8 mmol) and Et3N (10.4 mL) were added. The mixture was stirred at room temperature overnight, the volatiles were removed in vacuo and the resultant residue was suspended in water (500 mL) and sonicated for 15 minutes. The solid was isolated by vacuum filtration and the filter cake washed with water (100 mL) and acetone (25 mL) to give the title compound (A133) as a tan solid (5.92 g, 71%); LCMS-A: rt 6.895 min; m/z 445.1 [M−H]−.

Workup

  1. additionwere added
  2. stirringThe mixture was stirred at room temperature overnight
  3. customthe volatiles were removed in vacuo
  4. customsonicated for 15 minutes
  5. customThe solid was isolated by vacuum filtration
  6. washthe filter cake washed with water (100 mL) and acetone (25 mL)

Sources & evidence

ORD record
ord-5f8ab7776bd341a9932aef13c0e269cc
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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