Diisopropylethylamine → (S)-oxetan-3-yl 4-acetyl-3-methyl-7-(1-(oxetan-3-yl)-1H-pyrazol-4-yl)-3,4-dihydroquinoxaline-1(2H)-carboxylate

HRID 1485738Notes

Reaction equation

HRID 1485738 reaction equation
ClC(Cl)(O[C:5](=[O:11])[O:6][C:7](Cl)(Cl)Cl)Cl.[O:13]1[CH2:16]C(O)[CH2:14]1.C(N(CC)C(C)C)(C)C.[CH3:27][C@H:28]1[CH2:37][NH:36][C:35]2[C:30](=[CH:31][CH:32]=[C:33]([C:38]3[CH:39]=[N:40][N:41]([CH:43]4[CH2:46][O:45][CH2:44]4)[CH:42]=3)[CH:34]=2)[N:29]1[C:47](=[O:49])[CH3:48]>ClCCCl>[C:47]([N:29]1[C:30]2[C:35](=[CH:34][C:33]([C:38]3[CH:39]=[N:40][N:41]([CH:43]4[CH2:46][O:45][CH2:44]4)[CH:42]=3)=[CH:32][CH:31]=2)[N:36]([C:5]([O:6][CH:7]2[CH2:16][O:13][CH2:14]2)=[O:11])[CH2:37][C@@H:28]1[CH3:27])(=[O:49])[CH3:48]

Participants

6

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 94429TriphosgeneHCID 9942117Oxetan-3-olHCID 118079419(S)-1-(2-methyl-6-(1-(oxetan-3-yl)-1H-pyrazol-4-yl)-3,4-dihydroquinoxalin-1(2H)-yl)ethanone

Product 1

HCID 118078911(S)-oxetan-3-yl 4-acetyl-3-methyl-7-(1-(oxetan-3-yl)-1H-pyrazol-4-yl)-3,4-dihydroquinoxaline-1(2H)-carboxylateYield 63.1%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
50 °C

Procedure

Triphosgene (0.057 g, 0.192 mmol) was added to a solution of oxetan-3-ol (0.034 mL, 0.576 mmol) and N,N-diisopropylethylamine (0.101 mL, 0.576 mmol) in 1,2-dichloroethane (2.0 mL). The mixture stirred at rt for 30 min. (S)-1-(2-methyl-6-(1-(oxetan-3-yl)-1H-pyrazol-4-yl)-3,4-dihydroquinoxaline-1(2H)-yl)ethanone (0.030 g, 0.096 mmol) and N,N-diisopropylethylamine (0.101 mL, 0.576 mmol) were added and the mixture stirred at 50° C. for 3 h. The reaction mixture was concentrated to afford an orange oil. This material was purified via column chromatography on silica gel (Biotage 25 g column, gradient elution with 50-100% ethyl acetate-hexane then 5-10% methanol-dichloromethane) to afford (S)-oxetan-3-yl 4-acetyl-3-methyl-7-(1-(oxetan-3-yl)-1H-pyrazol-4-yl)-3,4-dihydroquinoxaline-1(2H)-carboxylate (0.025 g, 63%) as a tan solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 0.95 (d, J=6.74 Hz, 3 H), 2.10 (s, 3 H), 3.49 (br s, 1 H), 3.98 (br dd, J=12.90, 5.86 Hz, 1 H), 4.51 (ddd, J=10.55, 7.18, 5.42 Hz, 2 H), 4.66-4.79 (m, 2 H), 4.79-4.94 (m, 5 H), 5.30-5.45 (m, 1 H), 5.53 (dq, J=14.07, 7.23 Hz, 1 H), 7.30 (dd, J=8.35, 1.91 Hz, 1 H), 7.41 (br s, 1 H), 7.86-8.00 (m, 2 H), 8.25 (s, 1 H). MS (ESI, pos. ion) m/z 413.

Workup

  1. additionwere added
  2. concentrationThe reaction mixture was concentrated
  3. customto afford an orange oil
  4. customThis material was purified via column chromatography on silica gel (
  5. washBiotage 25 g column, gradient elution with 50-100% ethyl acetate-hexane

Sources & evidence

ORD record
ord-6f3f29b61d3d4f2da4ac02a6e43c89da
Source dataset
uspto-grants-2016_08
Patent number
US09422281B2

Reaction notes

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