Cyclopropanecarboxylic acid → (3aS,7aS)-1-[1-[1-(cyclopropanecarbonyl)-4-methyl-4-piperidyl]-4-piperidyl]-3a,4,5,6,7,7a-hexahydro-3H-benzoimidazol-2-one

HRID 1642475노트

반응식

HRID 1642475 반응식
[CH3:1][C:2]1([N:8]2[CH2:13][CH2:12][CH:11]([N:14]3[C@H:18]4[CH2:19][CH2:20][CH2:21][CH2:22][C@@H:17]4[NH:16][C:15]3=[O:23])[CH2:10][CH2:9]2)[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.[CH:24]1([C:27](O)=[O:28])[CH2:26][CH2:25]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C=O)C>[CH:24]1([C:27]([N:5]2[CH2:6][CH2:7][C:2]([N:8]3[CH2:13][CH2:12][CH:11]([N:14]4[C@H:18]5[CH2:19][CH2:20][CH2:21][CH2:22][C@@H:17]5[NH:16][C:15]4=[O:23])[CH2:10][CH2:9]3)([CH3:1])[CH2:3][CH2:4]2)=[O:28])[CH2:26][CH2:25]1

참가 물질

6

반응물 4

HCID 15655Cyclopropanecarboxylic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57619802(3aS,7aS)-1-[1-(4-methyl-4-piperidyl)-4-piperidyl]-3a,4,5,6,7,7a-hexahydro-3H-benzoimidazol-2-one

생성물 1

HCID 25221109(3aS,7aS)-1-[1-[1-(cyclopropanecarbonyl)-4-methyl-4-piperidyl]-4-piperidyl]-3a,4,5,6,7,7a-hexahydro-3H-benzoimidazol-2-one수율 61%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To the solution (3aS,7aS)-1-[1-(4-methyl-4-piperidyl)-4-piperidyl]-3a,4,5,6,7,7a-hexahydro-3H-benzoimidazol-2-one (99 mg, 0.25 mmol) in dry DMF (3 mL) was added cyclopropanecarboxylic acid (26 mg, 0.3 mmol) followed by HATU (114 mg, 0.3 mmol) and diisopropylethylamine (0.10 mL, 0.5 mmol) and stirred at room temperature for 1 h. The solvent was removed in vacuo, dichloromethane added (15 mL), washed with saturated NaHCO3 (10 mL) and brine (10 mL), dried over Na2SO4 and concentrated in vacuo. The residue was purified with preparative LC/MS (high pH) to yield the title compound (59 mg, 61%) as white powder. 1H NMR (400 MHz, METHANOL-D4) δ ppm 0.71-0.89 (m, 4H), 1.00 (s, 3H), 1.28-1.46 (m, 5H), 1.50-1.68 (m, 2H), 1.68-1.89 (m, 8H), 1.89-2.00 (m, 2H), 2.11-2.31 (m, 2H), 2.86-3.02 (m, 2H), 3.02-3.14 (m, 2H), 3.47-3.70 (m, 4H), 3.75-3.91 (m, 1H). MS (M+1): 389.2.

후처리

  1. customThe solvent was removed in vacuo, dichloromethane
  2. additionadded (15 mL)
  3. washwashed with saturated NaHCO3 (10 mL) and brine (10 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified with preparative LC/MS (high pH)

출처 및 근거

ORD 기록
ord-6e0235bcbc65470997525ecd5650c228
출처 데이터셋
uspto-grants-2012_02
특허 번호
US08119661B2

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