Methanol → HCID 44612494, compound

HRID 536391Notes

Reaction equation

HRID 536391 reaction equation
[Cl:1][C:2]1[C:3]([NH:23][C:24]2[CH:28]=[C:27]([CH3:29])[NH:26][N:25]=2)=[N:4][C:5]([NH:8][C:9]2[CH:14]=[C:13]([CH3:15])[C:12]([CH:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)=[CH:11][C:10]=2[F:22])=[N:6][CH:7]=1.CO.[O:32]1[CH2:37][CH2:36][C:35](=O)[CH2:34][CH2:33]1.[BH3-]C#N.[Na+]>C(Cl)Cl>[Cl:1][C:2]1[C:3]([NH:23][C:24]2[CH:28]=[C:27]([CH3:29])[NH:26][N:25]=2)=[N:4][C:5]([NH:8][C:9]2[CH:14]=[C:13]([CH3:15])[C:12]([CH:16]3[CH2:17][CH2:18][N:19]([CH:35]4[CH2:36][CH2:37][O:32][CH2:33][CH2:34]4)[CH2:20][CH2:21]3)=[CH:11][C:10]=2[F:22])=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 121599Tetrahydro-4H-pyran-4-oneHCID 5003444Sodium cyanoborohydrideHCID 446126165-chloro-N2-(2-fluoro-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine

Product 1

HCID 44612494HCID 44612494, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
60 °C

Procedure

To a suspension of 5-chloro-N2-(2-fluoro-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine (2.50 g, 6.0 mmol) in a mixed solvent of MeOH (42 mL) and DCM (10 mL) was added dihydro-2H-pyran-4(3H)-one (3.33 mL, 36.0 mmol) and TEA (8.36 mL, 60.0 mmol). The reaction mixture was heated at 60° C. for 1 h before NaCNBH3 (1.66 g, 26.4 mmol) was added. The mixture was heated at 60° C. for another 2 h, cooled down to room temperature, diluted with DCM (60 mL), dry loaded onto silica gel (12.5 g), and purified by silica gel chromatography (DCM with 1% NH3 to 10% MeOH in DCM with 1% NH3 gradient) to provide 5-chloro-N2-(2-fluoro-5-methyl-4-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)phenyl)-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine as a white solid; 1H NMR (DMSO-d6, 400 MHz) δ 12.08 (br, 1H), 9.58 (br, 1H), 8.65 (d, J=28.4 Hz, 1H), 8.02 (s, 1H), 7.36 (d, J=8.4 Hz, 1H), 7.03 (d, J=12.4 Hz, 1H), 6.08 (br, 1H), 3.89 (dd, J=10.8, 3.6 Hz, 2H), 3.28 (t, J=10.4 Hz, 2H), 2.99 (d, J=10.8 Hz, 2H), 2.64-2.43 (m, 2H), 2.24-2.15 (m, 8H), 1.71-1.40 (m, 8H); ESMS m/z 500.2 (M+H+).

Workup

  1. additionwas added
  2. temperaturecooled down to room temperature
  3. customdry loaded onto silica gel (12.5 g)
  4. custompurified by silica gel chromatography (DCM with 1% NH3 to 10% MeOH in DCM with 1% NH3 gradient)

Sources & evidence

ORD record
ord-fedf3ccc3e4640efb22ffa1a756960f1
Source dataset
uspto-grants-2014_10
Patent number
US08859574B2

Reaction notes

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