(S)-methyl 6-(1-(3-(benzyloxy)cyclobutyl)-1H-pyrazol-4-yl)-5-cyclobutoxy-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate → (S)-methyl 5-cyclobutoxy-6-(1-(3-hydroxycyclobutyl)-1H-pyrazol-4-yl)-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate

HRID 1051692Notes

Reaction equation

HRID 1051692 reaction equation
C([O:8][CH:9]1[CH2:12][CH:11]([N:13]2[CH:17]=[C:16]([C:18]3[C:19]([O:33][CH:34]4[CH2:37][CH2:36][CH2:35]4)=[C:20]4[C:25](=[CH:26][CH:27]=3)[N:24]([C:28]([O:30][CH3:31])=[O:29])[C@@H:23]([CH3:32])[CH2:22][CH2:21]4)[CH:15]=[N:14]2)[CH2:10]1)C1C=CC=CC=1>[Pd].CO>[CH:34]1([O:33][C:19]2[C:18]([C:16]3[CH:15]=[N:14][N:13]([CH:11]4[CH2:12][CH:9]([OH:8])[CH2:10]4)[CH:17]=3)=[CH:27][CH:26]=[C:25]3[C:20]=2[CH2:21][CH2:22][C@H:23]([CH3:32])[N:24]3[C:28]([O:30][CH3:31])=[O:29])[CH2:35][CH2:36][CH2:37]1

Participants

4

Reactant 1

HCID 118075687(S)-methyl 6-(1-(3-(benzyloxy)cyclobutyl)-1H-pyrazol-4-yl)-5-cyclobutoxy-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate

Product 1

HCID 118076270(S)-methyl 5-cyclobutoxy-6-(1-(3-hydroxycyclobutyl)-1H-pyrazol-4-yl)-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

Palladium on carbon (10 wt %, 0.060 g) was added to a solution of (S)-methyl 6-(1-(3-(benzyloxy)cyclobutyl)-1H-pyrazol-4-yl)-5-cyclobutoxy-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate (0.060 g, 0.12 mmol) in methanol (10 mL), and the resulting mixture stirred at room temperature under an atmosphere of hydrogen for 16 h. The reaction mixture was filtered, and the filtrate was concentrated under vacuum. The residue was purified by preparative-HPLC with the following conditions (Waters I): Column, XBridge Prep Shield RP18 OBD Column, 19×150 mm, 5 um; mobile phase, Water (0.05% ammonium bicarbonate) and acetonitrile (30% to 50% acetonitrile in 10 min, flow rate: 20 mL/min); Detector, UV254&220 nm. This afforded (S)-methyl 5-cyclobutoxy-6-(1-(3-hydroxycyclobutyl)-1H-pyrazol-4-yl)-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate (0.031 g, 63%) as a white solid. 1H NMR (300 MHz, CD3OD) δ ppm 1.16 (d, J=6.30 Hz, 3H), 1.32-1.51 (m, 2H), 1.55-1.68 (m, 1H), 2.00-2.33 (m, 5H), 2.33-2.58 (m, 3H), 2.76-2.84 (m, 2H), 2.93-3.01 (m, 1H), 3.77 (s, 3H), 4.12-4.19 (m, 1H), 4.51-4.64 (m, 2H), 4.99-5.08 (m, 1H), 7.24-7.35 (m, 2H), 7.86 (s, 1H), 8.04 (s, 1H). MS (ESI, pos. ion) m/z 412 [M+H]+.

Workup

  1. filtrationThe reaction mixture was filtered
  2. concentrationthe filtrate was concentrated under vacuum
  3. customThe residue was purified by preparative-HPLC with the following conditions (Waters I)
  4. custommobile phase, Water (0.05% ammonium bicarbonate) and acetonitrile (30% to 50% acetonitrile in 10 min, flow rate: 20 mL/min)

Sources & evidence

ORD record
ord-b560ba99d1b140a0a9bf2803f121d2d2
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

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