Tritium → methyl (S)-5-cyclobutoxy-6-(5-fluoro-1-(piperidin-4-yl)-1H-pyrazol-4-yl)-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate

HRID 1051743노트

반응식

HRID 1051743 반응식
[H][H].C([N:10]1[CH2:15][CH2:14][CH:13]([N:16]2[C:20]([F:21])=[C:19]([C:22]3[C:23]([O:37][CH:38]4[CH2:41][CH2:40][CH2:39]4)=[C:24]4[C:29](=[CH:30][CH:31]=3)[N:28]([C:32]([O:34][CH3:35])=[O:33])[C@@H:27]([CH3:36])[CH2:26][CH2:25]4)[CH:18]=[N:17]2)[CH2:12][CH2:11]1)C1C=CC=CC=1.[3H][3H]>CO.[OH-].[OH-].[Pd+2]>[CH:38]1([O:37][C:23]2[C:22]([C:19]3[CH:18]=[N:17][N:16]([CH:13]4[CH2:14][CH2:15][NH:10][CH2:11][CH2:12]4)[C:20]=3[F:21])=[CH:31][CH:30]=[C:29]3[C:24]=2[CH2:25][CH2:26][C@H:27]([CH3:36])[N:28]3[C:32]([O:34][CH3:35])=[O:33])[CH2:39][CH2:40][CH2:41]1

참가 물질

6

반응물 3

HCID 24824TritiumHCID 118075772(S)-methyl 6-(1-(1-benzylpiperidin-4-yl)-5-fluoro-1H-pyrazol-4-yl)-5-cyclobutoxy-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylateHCID 178418361HCID 178418361, 화합물

생성물 1

HCID 118086342methyl (S)-5-cyclobutoxy-6-(5-fluoro-1-(piperidin-4-yl)-1H-pyrazol-4-yl)-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate수율 58.1%

시약·촉매·용매 2

HCID 9942167Palladium hydroxide촉매HCID 887Methanol용매

실험 절차

Balloon filled hydrogen was charged into a nitrogen purged suspension of (S)-methyl 6-(1-(1-benzylpiperidin-4-yl)-5-fluoro-1H-pyrazol-4-yl)-5-cyclobutoxy-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate (15.0 mg, 0.028 mmol) and 20% palladium hydroxide on carbon (40 mg, 0.285 mmol) in methanol (10 mL). The reaction flask was backfilled with hydrogen 3 times. The reaction solution was then stirred under a hydrogen atmosphere for 2 hours. The flask was purged with nitrogen, and the reaction mixture was filtered through of Celite and the bed of Celite was washed with ethyl acetate (10 mL). The filtered solvent was then concentrated in vacuo. The crude product was added directly to a plug of silica gel and eluted with 30% ethyl acetate in methanol to afford methyl (S)-5-cyclobutoxy-6-(5-fluoro-1-(piperidin-4-yl)-1H-pyrazol-4-yl)-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate (7.2 mg, 58%) as an off-white solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.09 (d, J=6.45 Hz, 3H), 1.21-1.30 (m, 2H), 1.42-1.57 (m, 1H), 1.76-1.88 (m, 3H), 1.89-2.01 (m, 5H), 2.34-2.43 (m, 2H), 2.53-2.61 (m, 1H), 2.71-2.85 (m, 2H), 3.03 (br d, J=12.31 Hz, 1H), 3.13-3.21 (m, 1H), 3.68 (s, 3H), 3.95-4.05 (m, 1H), 4.15-4.30 (m, 1H), 4.41-4.52 (m, 1H), 7.14 (d, J=8.15 Hz, 1H), 7.29 (d, J=8.79 Hz, 1H), 7.61 (s, 1H). MS (ESI, pos. ion) m/z 443 [M+H]+.

후처리

  1. additionwas charged into a nitrogen
  2. custompurged
  3. customThe flask was purged with nitrogen
  4. filtrationthe reaction mixture was filtered through of Celite
  5. washthe bed of Celite was washed with ethyl acetate (10 mL)
  6. concentrationThe filtered solvent was then concentrated in vacuo
  7. additionThe crude product was added directly to a plug of silica gel
  8. washeluted with 30% ethyl acetate in methanol

출처 및 근거

ORD 기록
ord-7aefbbddab3d4d329b375299a9566408
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09388161B2

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