Nitrogen → Cyclopentyl(S)-2-{4-[6-Amino-5-(4-fluorobenzoyl)-2-oxo-2H-pyridin-1-yl]cyclohexyl amino}-3-phenylpropionate

HRID 1667374노트

반응식

HRID 1667374 반응식
[NH2:1][C:2]1[N:7]([CH:8]2[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]2)[C:6](=[O:15])[CH:5]=[CH:4][C:3]=1[C:16](=[O:24])[C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=1.[CH:25]1([O:30][C:31](=[O:41])[C@H:32]([CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[NH2:33])[CH2:29][CH2:28][CH2:27][CH2:26]1.N#N.[BH3-]C#N.[Na+]>CO.CC(O)=O>[NH2:1][C:2]1[N:7]([CH:8]2[CH2:13][CH2:12][CH:11]([NH:33][C@@H:32]([CH2:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[C:31]([O:30][CH:25]3[CH2:26][CH2:27][CH2:28][CH2:29]3)=[O:41])[CH2:10][CH2:9]2)[C:6](=[O:15])[CH:5]=[CH:4][C:3]=1[C:16](=[O:24])[C:17]1[CH:18]=[CH:19][C:20]([F:23])=[CH:21][CH:22]=1

참가 물질

7

반응물 4

HCID 947NitrogenHCID 5003444Sodium cyanoborohydrideHCID 53840847Cyclopentyl (2S)-2-amino-3-phenylpropanoateHCID 576584256-Amino-5-(4-fluorobenzoyl)-1-(4-oxo-cyclohexyl)-1H-pyridin-2-one

생성물 1

HCID 57658387Cyclopentyl(S)-2-{4-[6-Amino-5-(4-fluorobenzoyl)-2-oxo-2H-pyridin-1-yl]cyclohexyl amino}-3-phenylpropionate

시약·촉매·용매 2

HCID 176Acetic Acid용매HCID 887Methanol용매

실험 절차

Intermediate 6 (50 mg, 0.15 mmol) was added to a colourless solution of L-phenylalanine cyclopentyl ester (89 mg, 0.38 mmol) in MeOH (10 ml) at RT/N2 and stirred at RT for 1 h. AcOH glacial was added dropwise to adjust the pH to 6 followed by the NaCNBH3 (38 mg, 0.61 mmol). The resultant colourless solution was stirred at RT overnight and then carefully quenched with sat. NaHCO3 (20 ml) and extracted into CH2Cl2 (3×15 ml). The combined organic phases were washed with 2M HCl (2×20 ml), brine (20 ml), dried (Na2SO4), filtered and concentrated in vacuo giving a cream coloured solid. Purification by flash column chromatography (silica, gradient elution 40-100% EtOAc/heptane) gave the desired material, separable as two isomers, isomer 1 (Example 34) as a white solid (Yield=39 mg, 47%) LCMS purity 100%, m/z 546 [M+H]+, 1H NMR (400 MHz, CD3OD), δ: 1.40-2.05 (16H, m), 2.85-3.10 (3H, m), 3.60-3.70 (1H, m), 4.55-4.65 (1H, m), 5.10-5.20 (1H, m), 5.70 (1H, d), 7.15-7.40 (7H, m), 7.45-7.50 (1H, m), 7.50-7.60 (2H, m) and isomer 2 (Example 35) LCMS purity 97%, m/z 546 [M+H]+, 1H NMR (400 MHz, CD3OD), δ: 1.25-1.85 (12H, m), 1.95-2.20 (2H, m), 2.45-2.95 (4H, m), 3.00-3.10 (1H, m), 3.65-3.75 (1H, m), 4.55-4.65 (1H, m), 5.05-5.15 (1H, m), 5.65 (1H, d), 7.20-7.35 (7H, m), 7.40-7.50 (1H, m), 7.50-7.60 (2H, m) as a colourless film (Yield=15 mg, 18%).

후처리

  1. stirringThe resultant colourless solution was stirred at RT overnight
  2. customcarefully quenched with sat. NaHCO3 (20 ml)
  3. extractionextracted into CH2Cl2 (3×15 ml)
  4. washThe combined organic phases were washed with 2M HCl (2×20 ml), brine (20 ml)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customgiving a cream
  9. customPurification
  10. washby flash column chromatography (silica, gradient elution 40-100% EtOAc/heptane)

출처 및 근거

ORD 기록
ord-8b786c1b1b494c1185d0dc3996cb081e
출처 데이터셋
uspto-grants-2011_10
특허 번호
US08044211B2

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