Cesium carbonate → tert-butyl 4-(6-(5-chloro-4-(5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3-ylamino)pyrimidin-2-ylamino)-4-methylpyridin-3-yl)piperidine-1-carboxylate

HRID 2093818Notes

Reaction equation

HRID 2093818 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:13]=[C:12]([CH3:14])[N:11]([CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][O:16]3)[N:10]=2)[C:5]([Cl:21])=[CH:4][N:3]=1.[NH2:22][C:23]1[N:28]=[CH:27][C:26]([CH:29]2[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31][CH2:30]2)=[C:25]([CH3:42])[CH:24]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>C1COCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:21][C:5]1[C:6]([NH:8][C:9]2[CH:13]=[C:12]([CH3:14])[N:11]([CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][O:16]3)[N:10]=2)=[N:7][C:2]([NH:22][C:23]2[N:28]=[CH:27][C:26]([CH:29]3[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:40])([CH3:39])[CH3:41])=[O:36])[CH2:31][CH2:30]3)=[C:25]([CH3:42])[CH:24]=2)=[N:3][CH:4]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 582550552,5-Dichloro-N-(5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3-yl)pyrimidin-4-amineHCID 67168439Tert-butyl 4-(6-amino-4-methylpyridin-3-yl)piperidine-1-carboxylate

Product 1

HCID 67167118tert-butyl 4-(6-(5-chloro-4-(5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3-ylamino)pyrimidin-2-ylamino)-4-methylpyridin-3-yl)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of 2,5-dichloro-N-(5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3-yl)pyrimidin-4-amine (150 mg, 0.45 mmol), tert-butyl 4-(6-amino-4-methylpyridin-3-yl)piperidine-1-carboxylate (120 mg, 0.41 mmol), Xantphos (24 mg, 0.04 mmol) and cesium carbonate (270 mg, 0.82 mmol) in THF (4 mL) was added palladium acetate (5 mg, 0.02 mmol). The mixture was purged with nitrogen and the tube was sealed. The mixture was heated in an oil bath at 100° C. for 5 h. The mixture was filtered and concentrated. The residue was purified with silica chromatography (70% ethyl acetate in hexanes) to afford tert-butyl 4-(6-(5-chloro-4-(5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3-ylamino)pyrimidin-2-ylamino)-4-methylpyridin-3-yl)piperidine-1-carboxylate as a yellow solid; ESMS m/z 583 (M+H+).

Workup

  1. customThe mixture was purged with nitrogen
  2. customthe tube was sealed
  3. filtrationThe mixture was filtered
  4. concentrationconcentrated
  5. customThe residue was purified with silica chromatography (70% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-d6a86be445f84ea5aed8ea32cb7be10b
Source dataset
uspto-grants-2013_05
Patent number
US08445505B2

Reaction notes

Loading…