Formaldehyde → 2-[1-(1-Methyl-4-(tert-butyloxycarbonyl)piperazine-2-yl)-ethylamino]-4-[benzimidazol-1-yl]-pyrimidine

HRID 429293Notes

Reaction equation

HRID 429293 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH:10]([CH:14]([NH:16][C:17]2[N:22]=[C:21]([N:23]3[C:27]4[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=4[N:25]=[CH:24]3)[CH:20]=[CH:19][N:18]=2)[CH3:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[BH3-][C:33]#N.[Na+].C=O.O>CO.CC#N.CCOC(C)=O>[CH3:33][N:11]1[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:9][CH:10]1[CH:14]([NH:16][C:17]1[N:22]=[C:21]([N:23]2[C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=3[N:25]=[CH:24]2)[CH:20]=[CH:19][N:18]=1)[CH3:15]

Participants

8

Reactant 4

HCID 712FormaldehydeHCID 962WaterHCID 5003444Sodium cyanoborohydrideHCID 702154342-[1-(4-(Tert-butyloxycarbonyl)-piperazine-2-yl)-ethylamino]-4-(benzimidazol-1-yl)-pyrimidine

Product 1

HCID 183543432-[1-(1-Methyl-4-(tert-butyloxycarbonyl)piperazine-2-yl)-ethylamino]-4-[benzimidazol-1-yl]-pyrimidineYield 85.4%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-[1-(4-(tert-butyloxycarbonyl)piperazine-2-yl)-ethylamino]-4-(benzimidazol-1-yl)-pyrimidine (EXAMPLE 17, Step C; 17 mg) in 1 mL of MeOH and 1 mL of CH3CN was added NaBH3CN (5 mg) and 37% aqueous formaldehyde (20 μL). The mixture was stirred overnight at room temperature, then diluted with 5 mL of EtOAc and poured into 10 mL of water. The phases were separated and the aqueous phase was extracted with 2×5 mL of EtOAc. The aqueous phase was basified (pH>10) by addition of 5 N NaOH, then extracted with 5×5 mL of EtOAc. The combined organic extracts were washed with 5 mL of brine, dried over Na2SO4, and concentrated to yield 15 mg of the title compound.

Workup

  1. customThe phases were separated
  2. extractionthe aqueous phase was extracted with 2×5 mL of EtOAc
  3. additionby addition of 5 N NaOH
  4. extractionextracted with 5×5 mL of EtOAc
  5. washThe combined organic extracts were washed with 5 mL of brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-331fd465e6c74bb8b7f3607689911ab5
Source dataset
uspto-grants-2001_11
Patent number
US06316444B1

Reaction notes

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