Methanol → HCID 66970874, compound

HRID 1363164Notes

Reaction equation

HRID 1363164 reaction equation
[CH3:1][O:2][C:3]1[CH:41]=[C:40]([O:42][CH3:43])[CH:39]=[CH:38][C:4]=1[CH2:5][NH:6][C:7]1[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[CH:9][C:8]=1[NH:15][C:16]1[N:21]=[C:20]([NH:22][C@H:23]2[C:32]3[C:27](=[C:28]([F:34])[CH:29]=[C:30]([F:33])[CH:31]=3)[O:26][CH2:25][CH2:24]2)[C:19]([N+:35]([O-])=O)=[CH:18][N:17]=1.S(S([O-])=O)([O-])=O.[Na+].[Na+].C(=O)(O)[O-].[Na+].CO>C1COCC1.O.CCOC(C)=O>[CH3:1][O:2][C:3]1[CH:41]=[C:40]([O:42][CH3:43])[CH:39]=[CH:38][C:4]=1[CH2:5][NH:6][C:7]1[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[CH:9][C:8]=1[NH:15][C:16]1[N:21]=[C:20]([NH:22][C@H:23]2[C:32]3[C:27](=[C:28]([F:34])[CH:29]=[C:30]([F:33])[CH:31]=3)[O:26][CH2:25][CH2:24]2)[C:19]([NH2:35])=[CH:18][N:17]=1

Participants

8

Reactant 4

HCID 887MethanolHCID 24489Sodium DithioniteHCID 516892Sodium BicarbonateHCID 66970781HCID 66970781, compound

Product 1

HCID 66970874HCID 66970874, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (R)-4-(2,4-dimethoxybenzylamino)-3-(4-(6,8-difluorochroman-4-ylamino)-5-nitropyrimidin-2-ylamino)benzonitrile (358 mg) in THF (25 mL) was treated with a solution of sodium hydrosulfite (1.5 g) and sodium bicarbonate (1.5 g) in 20 mL of distilled water. Methanol (5 mL) was added to maintain a homogeneous solution. After 15 minutes, the mixture was diluted with EtOAc (100 mL) and washed with saturated aqueous NaCl (2×100 mL). The organic layer was separated, dried over Na2SO4, filtered, and concentrated in vacuo to provide the intermediate (R)-4-(2,4-dimethoxybenzylamino)-3-(5-amino-4-(6,8-difluorochroman-4-ylamino)pyrimidin-2-ylamino)benzonitrile. The intermediate was dissolved in THF (5 mL) and treated with carbonyldiimidazole (0.55 g) for 16 hours. The mixture was diluted with EtOAc (100 mL) and washed twice with saturated aqueous NaCl (2×100 mL). The organic layer was separated, dried over Na2SO4, filtered, and concentrated in vacuo. Column chromatography (2→3% MeOH/DCM) provided 230 mg of the title compound.

Workup

  1. temperatureto maintain a homogeneous solution
  2. washwashed with saturated aqueous NaCl (2×100 mL)
  3. customThe organic layer was separated
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-9f3f753d36364cf9b7b111963f44e349
Source dataset
uspto-grants-2011_02
Patent number
US07884109B2

Reaction notes

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