Hydrochloric Acid → methyl (S)-5-cyclobutoxy-6-(1-((3 S,4R)-3-fluoropiperidin-4-yl)-1H-pyrazol-4-yl)-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate

HRID 1051746Notes

Reaction equation

HRID 1051746 reaction equation
Cl.C(OC([N:9]1[CH2:14][CH2:13][C@@H:12]([N:15]2[CH:19]=[C:18]([C:20]3[C:21]([O:35][CH:36]4[CH2:39][CH2:38][CH2:37]4)=[C:22]4[C:27](=[CH:28][CH:29]=3)[N:26]([C:30]([O:32][CH3:33])=[O:31])[C@@H:25]([CH3:34])[CH2:24][CH2:23]4)[CH:17]=[N:16]2)[C@@H:11]([F:40])[CH2:10]1)=O)(C)(C)C>O1CCOCC1>[CH:36]1([O:35][C:21]2[C:20]([C:18]3[CH:17]=[N:16][N:15]([C@@H:12]4[CH2:13][CH2:14][NH:9][CH2:10][C@@H:11]4[F:40])[CH:19]=3)=[CH:29][CH:28]=[C:27]3[C:22]=2[CH2:23][CH2:24][C@H:25]([CH3:34])[N:26]3[C:30]([O:32][CH3:33])=[O:31])[CH2:37][CH2:38][CH2:39]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 118076351(S)-methyl 6-(1-((3 S,4R)-1-(tert-butoxycarbonyl)-3-fluoropiperidin-4-yl)-1H-pyrazol-4-yl)-5-cyclobutoxy-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate

Product 1

HCID 118086226methyl (S)-5-cyclobutoxy-6-(1-((3 S,4R)-3-fluoropiperidin-4-yl)-1H-pyrazol-4-yl)-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylateYield 47%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Hydrogen chloride (4.0 N in 1,4-dioxane, 0.23 mL, 0.931 mmol) was added to a solution of (S)-methyl 6-(1-((3S,4R)-1-(tert-butoxycarbonyl)-3-fluoropiperidin-4-yl)-1H-pyrazol-4-yl)-5-cyclobutoxy-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate (101 mg, 0.186 mmol) in 1,4-dioxane (1.0 mL), and the reaction mixture stirred at room temperature for 3 h. The reaction solution was concentrated under a stream of nitrogen, diluted with saturated aqueous sodium bicarbonate (1 mL) and extracted with ethyl acetate (3×1 mL). The combined organic layers were added directly to a plug of silica gel and eluted with 30% ethyl acetate in methanol to afford methyl (S)-5-cyclobutoxy-6-(1-((3S,4R)-3-fluoropiperidin-4-yl)-1H-pyrazol-4-yl)-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate (38 mg, 47%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.07 (d, J=6.45 Hz, 3H), 1.19-1.39 (m, 2H), 1.47-1.58 (m, 1H), 1.96-2.18 (m, 8H), 2.34-2.43 (m, 2H), 2.55-2.72 (m, 1H), 2.77-2.89 (m, 2H), 3.00-3.13 (m, 1H), 3.14 (br d, J=4.98 Hz, 1H), 3.65 (s, 3H), 4.02-4.12 (m, 1H), 4.37-4.49 (m, 1H), 4.78-4.94 (m, 1H), 7.21 (d, J=8.50 Hz, 1H), 7.32 (d, J=8.79 Hz, 1H), 7.83 (s, 1H), 8.02 (s, 1H). MS (ESI, pos. ion) m/z 443 [M+H]+.

Workup

  1. concentrationThe reaction solution was concentrated under a stream of nitrogen
  2. additiondiluted with saturated aqueous sodium bicarbonate (1 mL)
  3. extractionextracted with ethyl acetate (3×1 mL)
  4. additionThe combined organic layers were added directly to a plug of silica gel
  5. washeluted with 30% ethyl acetate in methanol

Sources & evidence

ORD record
ord-0b0b5ef25cf54563858659e2a73e267c
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

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