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 1051743Notes

Reaction equation

HRID 1051743 reaction equation
[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

Participants

6

Reactant 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, compound

Product 1

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

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent

Procedure

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]+.

Workup

  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

Sources & evidence

ORD record
ord-7aefbbddab3d4d329b375299a9566408
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

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