Diisopropylethylamine → (S)-N-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl)-3-phenyl-6,7,8,9-tetrahydro-5H-imidazo[1,5-a]azepine-1-carboxamide

HRID 75121

반응식

HRID 75121 반응식
[C:1]1([C:7]2[N:11]3[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][C:10]3=[C:9]([C:17]([OH:19])=O)[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:20][C@@H:21]([C:26]([CH3:29])([CH3:28])[CH3:27])[C:22]([NH:24][CH3:25])=[O:23].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>C(Cl)Cl>[CH3:27][C:26]([CH3:29])([CH3:28])[C@H:21]([NH:20][C:17]([C:9]1[N:8]=[C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[N:11]2[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][C:10]=12)=[O:19])[C:22]([NH:24][CH3:25])=[O:23]

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 445856(2S)-2-Amino-N,3,3-trimethylbutanamideHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 253421753-phenyl-6,7,8,9-tetrahydro-5H-imidazo[1,5-a]azepine-1-carboxylic acid2회

생성물 1

HCID 46234937(S)-N-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl)-3-phenyl-6,7,8,9-tetrahydro-5H-imidazo[1,5-a]azepine-1-carboxamide수율 89.2%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

3-phenyl-6,7,8,9-tetrahydro-5H-imidazo[1,5-a]azepine-1-carboxylic acid (Intermediate B1) (100 mg, 0.390 mmol) was dissolved in DCM (10 mL) in a 40 mL screw-cap vial. (S)-2-amino-N,3,3-trimethylbutanamide (59.1 mg, 0.410 mmol) and DIEA (204 μl, 1.171 mmol) were added, followed by TBTU (132 mg, 0.410 mmol), and the reaction was stirred for 3 hours. LCMS showed complete consumption of starting material. The solution was extracted with saturated aqueous sodium bicarbonate (10 mL) and the organic layer was removed. The aqueous layer was extracted with DCM (10 ml). The combined organic extracts were dried with anhydrous sodium sulfate, filtered and evaporated under reduced pressure to a brown oil which was purified by flash chromatography (silica gel, 25% Hex/EtOAc to 100% EtOAc). Fractions were combined to yield the desired (S)—N-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl)-3-phenyl-6,7,8,9-tetrahydro-5H-imidazo[1,5-a]azepine-1-carboxamide as a white solid (133 mg, 89%). LCMS (+ESI) m/z 383.2 [MH]+. 1H-NMR (CDCl3) δ 7.90 (d, 1H), 7.45-7.55 (m, 5H), 5.90 (m, 1H), 4.30 (d, 1H), 4.05 (m, 2H), 3.40 (m, 2H), 2.80 (d, 3H), 1.90 (m, 2H), 1.80 (m, 2H), 1.65 (m, 2H), 1.10 (s, 9H).

후처리

  1. customscrew-cap vial
  2. customconsumption of starting material
  3. extractionThe solution was extracted with saturated aqueous sodium bicarbonate (10 mL)
  4. customthe organic layer was removed
  5. extractionThe aqueous layer was extracted with DCM (10 ml)
  6. dry with materialThe combined organic extracts were dried with anhydrous sodium sulfate
  7. filtrationfiltered
  8. customevaporated under reduced pressure to a brown oil which
  9. customwas purified by flash chromatography (silica gel, 25% Hex/EtOAc to 100% EtOAc)

출처 및 근거

ORD 기록
ord-8b0e62b1b7984dd4984dfc3122c5d81f
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08835422B2

연결된 노트

불러오는 중…