Pyridine → (S)-1-(4-acetyl-3-methyl-7-(1-(oxetan-3-yl)-1H-pyrazol-4-yl)-3,4-dihydroquinoxalin-1(2H)-yl)-3-methylbutan-1-one

HRID 1485759Notes

Reaction equation

HRID 1485759 reaction equation
[CH3:1][C@H:2]1[CH2:11][NH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:12]3[CH:13]=[N:14][N:15]([CH:17]4[CH2:20][O:19][CH2:18]4)[CH:16]=3)[CH:8]=2)[N:3]1[C:21](=[O:23])[CH3:22].[CH3:24][CH:25]([CH3:30])[CH2:26][C:27](Cl)=[O:28].N1C=CC=CC=1>ClCCl>[C:21]([N:3]1[C:4]2[C:9](=[CH:8][C:7]([C:12]3[CH:13]=[N:14][N:15]([CH:17]4[CH2:20][O:19][CH2:18]4)[CH:16]=3)=[CH:6][CH:5]=2)[N:10]([C:27](=[O:28])[CH2:26][CH:25]([CH3:30])[CH3:24])[CH2:11][C@@H:2]1[CH3:1])(=[O:23])[CH3:22]

Participants

5

Reactant 3

HCID 1049PyridineHCID 66054Isovaleryl chlorideHCID 118079419(S)-1-(2-methyl-6-(1-(oxetan-3-yl)-1H-pyrazol-4-yl)-3,4-dihydroquinoxalin-1(2H)-yl)ethanone

Product 1

HCID 118079028(S)-1-(4-acetyl-3-methyl-7-(1-(oxetan-3-yl)-1H-pyrazol-4-yl)-3,4-dihydroquinoxalin-1(2H)-yl)-3-methylbutan-1-oneYield 42.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A 100-mL round-bottom flask was charged with (S)-1-(2-methyl-6-(1-(oxetan-3-yl)-1H-pyrazol-4-yl)-3,4-dihydroquinoxaline-1(2H)-yl)ethanone (50 mg, 0.16 mmol), 3-methylbutanoyl chloride (93 mg, 0.77 mmol), pyridine (63 mg, 0.80 mmol, 5.00 equiv) and dichloromethane (30 mL). The resulting solution stirred for 30 min at 0° C. in a water/ice bath and an additional 3 h at room temperature. The reaction mixture was concentrated under vacuum. The residue was purified by column chromatography on silica gel (eluting with 2-50% ethyl acetate-petroleum ether) to afford (S)-1-(4-acetyl-3-methyl-7-(1-(oxetan-3-yl)-1H-pyrazol-4-yl)-3,4-dihydroquinoxaline-1(2H)-yl)-3-methylbutan-1-one (26.7 mg, 42%) of as light yellow oil. 1H NMR (300 MHz, CD3OD) δ ppm 079 (br s, 3 H), 0.93 (d, J=6.60 Hz, 3 H), 1.18 (d, J=6.30 Hz, 3 H), 1.90-2.10 (m, 1 H), 2.42 (s, 3 H), 2.35-2.43 (m, 1 H), 2.48-2.50 (m, 1 H), 2.51-2.89 (m, 1 H), 4.80-4.95 (m, 2 H), 5.08 (d, J=6.90 Hz, 4 H), 5.55-5.65 (m, 1 H), 7.38-7.45 (m, 1 H), 7.55-7.75 (m, 2 H), 8.03 (s, 1 H), 8.24 (s, 1 H). MS (ESI, pos. ion) m/z 425 [M+H]+.

Workup

  1. concentrationThe reaction mixture was concentrated under vacuum
  2. customThe residue was purified by column chromatography on silica gel (eluting with 2-50% ethyl acetate-petroleum ether)

Sources & evidence

ORD record
ord-e37180bf216140899b172d65f79d82a2
Source dataset
uspto-grants-2016_08
Patent number
US09422281B2

Reaction notes

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