Acetic Acid → tert-Butyl (2-{[4-(1-{1,3-dimethyl-1H-pyrazol-4-ylmethyl}piperidin-4-yl)benzoyl]amino}phenyl)carbamate

HRID 222408노트

반응식

HRID 222408 반응식
[NH:1]1[CH2:6][CH2:5][CH:4]([C:7]2[CH:29]=[CH:28][C:10]([C:11]([NH:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:12])=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.[CH3:30][N:31]1[CH:35]=[C:34]([CH:36]=O)[C:33]([CH3:38])=[N:32]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>ClCCl.C(OCC)C>[CH3:30][N:31]1[CH:35]=[C:34]([CH2:36][N:1]2[CH2:6][CH2:5][CH:4]([C:7]3[CH:29]=[CH:28][C:10]([C:11]([NH:13][C:14]4[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=4[NH:20][C:21](=[O:27])[O:22][C:23]([CH3:25])([CH3:26])[CH3:24])=[O:12])=[CH:9][CH:8]=3)[CH2:3][CH2:2]2)[C:33]([CH3:38])=[N:32]1

참가 물질

8

반응물 5

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 8472851,3-dimethyl-1H-pyrazole-4-carbaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 59830875Tert-butyl 2-[(4-piperidin-4-ylbenzoyl)amino]phenylcarbamate

생성물 1

HCID 59830877tert-Butyl (2-{[4-(1-{1,3-dimethyl-1H-pyrazol-4-ylmethyl}piperidin-4-yl)benzoyl]amino}phenyl)carbamate수율 87.3%

시약·촉매·용매 2

HCID 3283Diethyl Ether용매HCID 6344Dichloromethane용매2회

실험 절차

tert-Butyl 2-[(4-piperidin-4-ylbenzoyl)amino]phenylcarbamate (6.83 g, 17.3 mmol) and 1,3-dimethyl-1H-pyrazole-4-carbaldehyde (3.0 g, 24.2 mmol) were dissolved in dichloromethane (150 ml). Acetic acid (996 μl, 17.3 mmol) was then added and the reaction mixture allowed to stir at room temperature for four hours. Sodium triacetoxyborohydride (5.49 g, 25.9 mmol) was then added and reaction mixture stirred for a further 18 hours. Saturated aqueous sodium bicarbonate solution (300 ml) was then carefully added followed by dichloromethane (100 ml). The organic layer was separated and the aqueous layer re-extracted with more dichloromethane (150 ml). The combined organic extracts were dried over magnesium sulphate, filtered and evaporated to dryness. The residue obtained was purified by flash chromatography on silica, eluting with a 5% (v/v) solution of methanol in dichloromethane followed by a rising gradient of 5-10% (v/v) methanol in dichloromethane to afford a clear gum, which was taken up in diethyl ether and evaporated to dryness to afford the title compound (7.61 g, 87%); NMR Spectrum: (DMSO d6) δ 1.43 (s, 9H), 1.69 (m, 4H), 1.98 (m, 2H), 2.10 (s, 3H), 2.56 (m, 1H), 2.92 (m, 2H), 3.26 (s, 2H), 3.70 (s, 3H), 7.15 (m, 2H), 7.40 (m, 3H), 7.52 (m, 2H), 7.87 (d, 2H), 8.60 (s, 1H), 9.73 (s, 1H); Mass Spectrum: M+H+504.

후처리

  1. customreaction mixture
  2. stirringstirred for a further 18 hours
  3. customThe organic layer was separated
  4. extractionthe aqueous layer re-extracted with more dichloromethane (150 ml)
  5. dry with materialThe combined organic extracts were dried over magnesium sulphate
  6. filtrationfiltered
  7. customevaporated to dryness
  8. customThe residue obtained
  9. customwas purified by flash chromatography on silica
  10. washeluting with a 5% (v/v) solution of methanol in dichloromethane
  11. customto afford a clear gum, which
  12. customevaporated to dryness

출처 및 근거

ORD 기록
ord-fa6677272b7d458b9add8b27912cded5
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08207202B2

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