Sodium Bicarbonate → 5-{1-tert-Butyl-2-[2-(4-chloro-pyrazol-1-yl)-5-methoxy-phenyl]-1H-benzimidazol-5-yl}-pyrimidin-2-ylamine

HRID 1966709Notes

Reaction equation

HRID 1966709 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]([NH2:19])[C:11]([NH:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[CH:12][CH:13]=2)=[CH:4][N:3]=1.[Cl:20][C:21]1[CH:22]=[N:23][N:24]([C:26]2[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][C:27]=2[CH:28]=O)[CH:25]=1.C([O-])(O)=O.[Na+]>C(O)(=O)C>[C:15]([N:14]1[C:11]2[CH:12]=[CH:13][C:8]([C:5]3[CH:4]=[N:3][C:2]([NH2:1])=[N:7][CH:6]=3)=[CH:9][C:10]=2[N:19]=[C:28]1[C:27]1[CH:30]=[C:31]([O:34][CH3:35])[CH:32]=[CH:33][C:26]=1[N:24]1[CH:25]=[C:21]([Cl:20])[CH:22]=[N:23]1)([CH3:16])([CH3:18])[CH3:17]

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 585418994-(2-amino-pyrimidin-5-yl)-N1-tert-butyl-benzene-1,2-diamineHCID 585420082-(4-Chloro-pyrazol-1-yl)-5-methoxy-benzaldehyde

Product 1

HCID 532362565-{1-tert-Butyl-2-[2-(4-chloro-pyrazol-1-yl)-5-methoxy-phenyl]-1H-benzimidazol-5-yl}-pyrimidin-2-ylamineYield 27.1%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A solution of 4-(2-amino-pyrimidin-5-yl)-N1-tert-butyl-benzene-1,2-diamine (180 mg, 0.70 mmol) and 2-(4-chloro-pyrazol-1-yl)-5-methoxy-benzaldehyde (270 mg, 1.14 mmol) in acetic acid (5 mL) is warmed to 100° C. for 16 hours, then cooled to room temperature and neutralized with NaHCO3 (sat.). The product is extracted into EtOAc (3×) and the combined organics are dried (MgSO4), filtered and concentrated. Purification via flash chromatography (12 g silica gel, 0-5% MeOH/CH2Cl2) follows by reverse phase HPLC (20-100% CH3CN/H2O, each solvent containing 0.1% TFA) affords the title compound (90 mg, 27%). LCMS (ESMS): m/z 474.20 (M++1)

Workup

  1. extractionThe product is extracted into EtOAc (3×)
  2. dry with materialthe combined organics are dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification via flash chromatography (12 g silica gel, 0-5% MeOH/CH2Cl2)
  6. additioneach solvent containing 0.1% TFA)

Sources & evidence

ORD record
ord-785199d1e1d64b5baac2d5f7bc45d136
Source dataset
uspto-grants-2013_04
Patent number
US08420655B2

Reaction notes

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