Acetic Acid → (R)-3-[[N-(2-amino-5-trifluoromethylbenzoyl)glycyl]amino]-1-(2,4-dimethoxypyrimidin-5-ylmethyl)pyrrolidine

HRID 279265

Reaction equation

HRID 279265 reaction equation
[NH2:1][C:2]1[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][C:3]=1[C:4]([NH:6][CH2:7][C:8]([NH:10][C@@H:11]1[CH2:15][CH2:14][NH:13][CH2:12]1)=[O:9])=[O:5].[CH3:24][O:25][C:26]1[N:31]=[C:30]([O:32][CH3:33])[C:29]([CH:34]=O)=[CH:28][N:27]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>C1COCC1>[NH2:1][C:2]1[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:21])[F:22])=[CH:16][C:3]=1[C:4]([NH:6][CH2:7][C:8]([NH:10][C@@H:11]1[CH2:15][CH2:14][N:13]([CH2:34][C:29]2[C:30]([O:32][CH3:33])=[N:31][C:26]([O:25][CH3:24])=[N:27][CH:28]=2)[CH2:12]1)=[O:9])=[O:5]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5977822,4-Dimethoxypyrimidine-5-carbaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 54328411(R)-3-[[N-(2-Amino-5-trifluoromethylbenzoyl)glycyl]amino]pyrrolidine

Product 1

HCID 69214846(R)-3-[[N-(2-amino-5-trifluoromethylbenzoyl)glycyl]amino]-1-(2,4-dimethoxypyrimidin-5-ylmethyl)pyrrolidine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(R)-3-[{N-(2-Amino-5-trifluoromethylbenzoyl)glycyl}amino]pyrrolidine (17.2 mg, 0.04 mmol) was dissolved in THF (1 mL) and 2,4-dimethoxy-5-pyrimidine carboxaldehyde (6.7 mg, 0.04 mmol) was added followed by sodium triacetoxyborohydride (12.7 mg, 0.06 mmol) and glacial acetic acid (2.4 mg, 0.04 mmol). The mixture was stirred at room temperature for 24 h and evaporated. The residue was then dissolved in dichloromethane (1 mL) and washed with 1 N NaOH solution (1 mL). The organic phase was recovered and evaporated then treated with 25% trifluoroacetic acid in dichloromethane (1 mL) for 1 h at room temperature and evaporated. The residue was purified using LC/MS to afford (R)-3-[{N-(2-amino-5-trifluoromethylbenzoyl)glycyl}amino]-1-(2,4-dimethoxypyrimidin-5-ylmethyl)pyrrolidine (Compound No. 2175) (18.6 mg, 78%): The purity was determined by RPLC/MS (98%); ESI/MS m/e 483 (M++H, C21H25F3N6O4).

Workup

  1. customevaporated
  2. dissolutionThe residue was then dissolved in dichloromethane (1 mL)
  3. washwashed with 1 N NaOH solution (1 mL)
  4. customThe organic phase was recovered
  5. customevaporated
  6. additionthen treated with 25% trifluoroacetic acid in dichloromethane (1 mL) for 1 h at room temperature
  7. customevaporated
  8. customThe residue was purified

Sources & evidence

ORD record
ord-9337760ceef64ab69818a1e46be8bf15
Source dataset
uspto-grants-2002_03
Patent number
US06362177B1

Linked notes

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