5-Bromo-2-(trifluoromethyl)pyrimidine → HCID 86690350, compound

HRID 2409925Notes

Reaction equation

HRID 2409925 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][CH:3]([NH:7][C@@H:8]2[CH2:13][CH2:12][CH2:11][CH2:10][C@H:9]2[NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:2]1.Br[C:23]1[CH:24]=[N:25][C:26]([C:29]([F:32])([F:31])[F:30])=[N:27][CH:28]=1>CC(N(C)C)=O>[F:30][C:29]([F:32])([F:31])[C:26]1[N:27]=[CH:28][C:23]([N:1]2[CH2:6][CH2:5][CH2:4][CH:3]([NH:7][C@@H:8]3[CH2:13][CH2:12][CH2:11][CH2:10][C@H:9]3[NH:14][C:15](=[O:21])[O:16][C:17]([CH3:18])([CH3:20])[CH3:19])[CH2:2]2)=[CH:24][N:25]=1

Participants

4

Reactant 2

HCID 336979635-Bromo-2-(trifluoromethyl)pyrimidineHCID 71233145HCID 71233145, compound

Product 1

HCID 86690350HCID 86690350, compoundYield 44.3%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

Dimethylacetamide (5.25 mL) was added to a round bottom flask containing tert-butyl (1R,2R)-2-(piperidin-3-ylamino)cyclohexylcarbamate (0.47 gm, 1.58 mmol) and 5-bromo-2-(trifluoromethyl)pyrimidine (0.43 gm, 1.89 mmol). The reaction mixture was then heated at 100° C. After 48 h heating was stopped. The reaction mixture was partitioned between EtOAc and sat. NaHCO3. The organic phase was isolated, washed with saturated aqueous NaCl, dried over MgSO4, filtered and concentrated. The resulting residue was purified using silica gel chromatography eluting with a gradient of 0-100% EtOAc/Hexanes holding at 100% EtOAc to give the diastereomeric product, tert-butyl (1R,2R)-2-(1-(2-(trifluoromethyl)pyrimidin-5-yl)piperidin-3-ylamino)cyclohexylcarbamate, (0.31 gm, 0.70 mmol, 44% yield) as light yellow solid. Anal. Calcd. for C21H32F3N5O2 m/z 443.3, found: 444.3 (M+H)+.

Workup

  1. temperatureAfter 48 h heating
  2. customThe reaction mixture was partitioned between EtOAc and sat. NaHCO3
  3. customThe organic phase was isolated
  4. washwashed with saturated aqueous NaCl
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting residue was purified
  9. washeluting with a gradient of 0-100% EtOAc/Hexanes holding at 100% EtOAc

Sources & evidence

ORD record
ord-6cd57cdc9f4c44a49bd0de4617de9c91
Source dataset
uspto-grants-2014_08
Patent number
US08815909B2

Reaction notes

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