Acetic Acid → 2-(S)-{[2-Chloro-4-(4-methoxy-phenoxy)-pyrimidin-5-ylamino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1894142ノート

反応式

HRID 1894142 の反応式
[Cl:1][C:2]1[N:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=2)[C:5]([NH2:17])=[CH:4][N:3]=1.[C:18]([N:25]1[CH2:31][CH2:30][CH2:29][C@H:26]1[CH:27]=O)([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19].C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.C(Cl)Cl>[C:21]([O:20][C:18]([N:25]1[CH2:31][CH2:30][CH2:29][C@H:26]1[CH2:27][NH:17][C:5]1[C:6]([O:8][C:9]2[CH:10]=[CH:11][C:12]([O:15][CH3:16])=[CH:13][CH:14]=2)=[N:7][C:2]([Cl:1])=[N:3][CH:4]=1)=[O:19])([CH3:24])([CH3:22])[CH3:23]

参加物

7

反応物 4

HCID 176Acetic AcidHCID 2734674tert-butyl (2S)-2-formylpyrrolidine-1-carboxylate2 回HCID 5049666Sodium triacetoxyborohydrideHCID 58243054HCID 58243054、化合物

生成物 1

HCID 582430462-(S)-{[2-Chloro-4-(4-methoxy-phenoxy)-pyrimidin-5-ylamino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl ester収率 85%

試薬・触媒・溶媒 2

HCID 111,2-Dichloroethane溶媒HCID 6344Dichloromethane溶媒

実験手順

To a solution of Compound 1c (4.45 g, 17.7 mmol) in 1,2-dichloroethane (80 mL) was added Boc-L-prolinal (Compound 1d) (5.0 g; 24.4 mmol) and glacial acetic acid (4.5 mL) at ambient temperature, and the mixture was stirred under a nitrogen atmosphere for 3 h. The mixture was then treated with NaB(OAc)3H (9.37 g; 44.2 mmol) and continually stirred at room temperature for 20 h. The resultant mixture was diluted with CH2Cl2, and washed with saturated NaHCO3 (aq) and H2O. The organic phase was washed sequentially with H2O and brine, and then dried over Na2SO4. The mixture was filtered and the filtrate was evaporated under reduced pressure to give the crude material. The crude material was purified by flash column chromatography (SiO2), eluting with a Et2O—CH2Cl2 gradient to afford Compound 1e (6.54 g; 85% yield) as a pale-yellow solid. 1H-NMR (400 MHz, CDCl3): δ 7.73-7.79 (m, 1H), 7.07-7.14 (m, 2H), 6.91-6.98 (m, 2H), 5.73 (br. s, 0.6H), 4.77 (br. s, 0.4H), 4.20-4.30 (m, 1H), 3.85 (s, 3H), 3.21-3.58 (m, 4H), 1.81-2.11 (m, 4H), 1.46-1.49 (m, 9H); MS: m/z 435.1 (M+H)+.

後処理

  1. stirringcontinually stirred at room temperature for 20 h
  2. washwashed with saturated NaHCO3 (aq) and H2O
  3. washThe organic phase was washed sequentially with H2O and brine
  4. dry with materialdried over Na2SO4
  5. filtrationThe mixture was filtered
  6. customthe filtrate was evaporated under reduced pressure
  7. customto give the crude material
  8. customThe crude material was purified by flash column chromatography (SiO2)
  9. washeluting with a Et2O—CH2Cl2 gradient

出典と根拠

ORDレコード
ord-6dcc8a4d941445ee9bdfc236028c44e3
出典データセット
uspto-grants-2013_08
特許番号
US08513271B2

反応ノート

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