Sodium Bicarbonate → (S)-tert-butyl (1-((3-(((2-((3-fluorophenyl)amino)-4-(propylamino)pyrimidin-5-yl)methyl)amino)phenyl)amino)-1-oxopropan-2-yl)(methyl)carbamate

HRID 2284705Notes

Reaction equation

HRID 2284705 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([NH:8][C:9](=[O:21])[C@@H:10]([N:12]([CH3:20])[C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[CH3:11])[CH:5]=[CH:6][CH:7]=1.[F:22][C:23]1[CH:24]=[C:25]([NH:29][C:30]2[N:35]=[C:34]([NH:36][CH2:37][CH2:38][CH3:39])[C:33]([CH:40]=O)=[CH:32][N:31]=2)[CH:26]=[CH:27][CH:28]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>C(Cl)Cl.C(OCC)(=O)C.C(O)(=O)C>[F:22][C:23]1[CH:24]=[C:25]([NH:29][C:30]2[N:35]=[C:34]([NH:36][CH2:37][CH2:38][CH3:39])[C:33]([CH2:40][NH:1][C:2]3[CH:3]=[C:4]([NH:8][C:9](=[O:21])[C@@H:10]([N:12]([CH3:20])[C:13](=[O:19])[O:14][C:15]([CH3:17])([CH3:16])[CH3:18])[CH3:11])[CH:5]=[CH:6][CH:7]=3)=[CH:32][N:31]=2)[CH:26]=[CH:27][CH:28]=1

Participants

8

Reactant 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 90051717(S)-tert-butyl (1-((3-aminophenyl)amino)-1-oxopropan-2-yl)(methyl)carbamateHCID 90051747HCID 90051747, compound

Product 1

HCID 90051751(S)-tert-butyl (1-((3-(((2-((3-fluorophenyl)amino)-4-(propylamino)pyrimidin-5-yl)methyl)amino)phenyl)amino)-1-oxopropan-2-yl)(methyl)carbamateYield 68.4%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (S)-tert-butyl (1-((3-aminophenyl)amino)-1-oxopropan-2-yl)(methyl)carbamate (B9, 28 mg) and 2-((3-fluorophenyl)amino)-4-(propylamino)pyrimidine-5-carbaldehyde (E14, 24 mg) in methylene chloride (2 mL), sodium triacetoxyborohydride (28 mg) and acetic acid (50 μL) were added at room temperature, and the mixture was stirred at the same temperature for 5 hours. To the reaction mixture, ethyl acetate and saturated aqueous sodium hydrogencarbonate were added. The organic layer was separated, washed with saturated aqueous sodium chloride, and then dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent, 60 to 0% hexane in ethyl acetate) to obtain (S)-tert-butyl (1-((3-(((2-((3-fluorophenyl)amino)-4-(propylamino)pyrimidin-5-yl)methyl)amino)phenyl)amino)-1-oxopropan-2-yl)(methyl)carbamate (E18, 33 mg).

Workup

  1. customThe organic layer was separated
  2. washwashed with saturated aqueous sodium chloride
  3. dry with materialdried over anhydrous sodium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe obtained residue was purified by silica gel column chromatography (eluent, 60 to 0% hexane in ethyl acetate)

Sources & evidence

ORD record
ord-84c718960f5641778707bde83a72b0c0
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

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