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

HRID 133565

反応式

HRID 133565 の反応式
[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]

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
50 °C

実験手順

(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-pyrimidinecarboxaldehyde (6.7 mg, 0.04 mmol) was added to the resulting solution. Sodium triacetoxyborohydride (12.7 mg, 0.06 mmol) and glacial acetic acid (2.4 mg, 0.04 mmol) were subsequently added to the mixture. The resulting mixture was stirred at 50° C. for 24 hours and then concentrated. The residue was dissolved in dichloromethane (1 mL) and washed with a 1 M aqueous solution (1 mL) of NaOH. The organic layer was collected and concentrated, and a dichloromethane solution of 25% trifluoroacetic acid (1 mL) was added. The resulting mixture was stirred at room temperature for 1 hour and then concentrated. The obtained residue was purified by HPLC to thereby provide (R)-3-[[N-(2-amino-5-trifluoromethylbenzoyl)glycyl]amino]-1-(2,4-dimethoxypyrimidin-5-ylmethyl)pyrrolidine (Compd. No. 2175) (18.6 mg, 78%). The purity was determined by RPLC/MS (98%). ESI/MS m/e 483 (M++H, C21H25F3N6O4).

後処理

  1. concentrationconcentrated
  2. dissolutionThe residue was dissolved in dichloromethane (1 mL)
  3. washwashed with a 1 M aqueous solution (1 mL) of NaOH
  4. customThe organic layer was collected
  5. concentrationconcentrated
  6. additiona dichloromethane solution of 25% trifluoroacetic acid (1 mL) was added
  7. stirringThe resulting mixture was stirred at room temperature for 1 hour
  8. concentrationconcentrated
  9. customThe obtained residue was purified by HPLC to thereby provide (R)-3-[[N-(2-amino-5-trifluoromethylbenzoyl)glycyl]amino]-1-(2,4-dimethoxypyrimidin-5-ylmethyl)pyrrolidine (Compd. No

出典と根拠

ORDレコード
ord-7a64db8d4f464385a275ee2fe18c2301
出典データセット
uspto-grants-2008_06
特許番号
US07390830B1

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