Triethylamine → tert-Butyl N-[1-[3-[5-[2-(4-isopropylsulfonylphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]isoxazol-3-yl]phenyl]ethyl]carbamate

HRID 467506Notes

Reaction equation

HRID 467506 reaction equation
[C:1]([C:3]1[C:11]2[C:6](=[N:7][CH:8]=[C:9]([C:12]3[CH:17]=[CH:16][C:15]([S:18]([CH:21]([CH3:23])[CH3:22])(=[O:20])=[O:19])=[CH:14][CH:13]=3)[N:10]=2)[NH:5][CH:4]=1)#[CH:2].Cl[C:25](=[N:42][OH:43])[C:26]1[CH:27]=[C:28]([CH:32]([NH:34][C:35](=[O:41])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38])[CH3:33])[CH:29]=[CH:30][CH:31]=1.C(N(CC)CC)C>C1COCC1>[CH:21]([S:18]([C:15]1[CH:14]=[CH:13][C:12]([C:9]2[N:10]=[C:11]3[C:3]([C:1]4[O:43][N:42]=[C:25]([C:26]5[CH:27]=[C:28]([CH:32]([NH:34][C:35](=[O:41])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38])[CH3:33])[CH:29]=[CH:30][CH:31]=5)[CH:2]=4)=[CH:4][NH:5][C:6]3=[N:7][CH:8]=2)=[CH:17][CH:16]=1)(=[O:20])=[O:19])([CH3:23])[CH3:22]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 76686640Tert-butyl 1-(3-(chloro(hydroxyimino)methyl)phenyl)ethylcarbamateHCID 866624437-Ethynyl-2-(4-isopropylsulfonylphenyl)-5H-pyrrolo[2,3-b]pyrazine

Product 1

HCID 136340567tert-Butyl N-[1-[3-[5-[2-(4-isopropylsulfonylphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]isoxazol-3-yl]phenyl]ethyl]carbamateYield 64%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 7-ethynyl-2-(4-isopropylsulfonylphenyl)-5H-pyrrolo[2,3-b]pyrazine (72 mg, 0.2213 mmol) and tert-butyl 1-(3-(chloro(hydroxyimino)methyl)phenyl)ethylcarbamate (66.12 mg, 0.2213 mmol) in THF (2.5 mL) was added triethylamine (26.88 mg, 37.02 μL, 0.2656 mmol) The mixture was stirred at ambient temperature for 45 minutes then heated at 65° C. for 3.5 hours. The reaction was cooled to ambient temperature and the solvent removed in vacuo. The residues was dissolved in warm DCM (50 mL) and washed with saturated aqueous NaHCO3(×1), dried (MgSO4), filtered and concentrated in vacuo. The residue triturated from hot MeCN and the precipitate obtained on cooling was isolated by filtration and washed with MeCN to give the sub-title compound as a pale yellow powder (83 mg, 64% Yield). 1H NMR (400 MHz, DMSO) δ 1.28 (d, 6H), 1.41-1.45 (m, 3H), 1.43 (s, 9H), 3.58 (sept, 1H), 4.79 (br t, 1H), 7.52-7.62 (m, 4H), 7.92 (d, 1H), 8.00 (s, 1H), 8.10 (d, 2H), 8.68 (d, 2H), 8.76 (s, 1H), 9.25 (s, 1H) and 13.08 (br s, 1H) ppm; MS (ES) 588.1.

Workup

  1. temperaturethen heated at 65° C. for 3.5 hours
  2. temperatureThe reaction was cooled to ambient temperature
  3. customthe solvent removed in vacuo
  4. dissolutionThe residues was dissolved in warm DCM (50 mL)
  5. washwashed with saturated aqueous NaHCO3(×1)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue triturated from hot MeCN
  10. customthe precipitate obtained
  11. temperatureon cooling
  12. customwas isolated by filtration
  13. washwashed with MeCN

Sources & evidence

ORD record
ord-48ac28b9e9d441868ae18cbea291a58e
Source dataset
uspto-grants-2014_01
Patent number
US08623869B2

Reaction notes

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