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Triethylamine → tert-butyl N-[[4-[5-[6-(4-isopropylsulfonylphenyl)pyrazin-2-yl]isoxazol-3-yl]phenyl]methyl]-N-methyl-carbamate

HRID 522533
Notes
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Reaction equation

HRID 522533 reaction equation
C1C(=O)N(Cl)C(=O)C1.[OH:9][N:10]=[CH:11][C:12]1[CH:27]=[CH:26][C:15]([CH2:16][N:17]([CH3:25])[C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[CH:14][CH:13]=1.[C:28]([C:30]1[CH:35]=[N:34][CH:33]=[C:32]([C:36]2[CH:41]=[CH:40][C:39]([S:42]([CH:45]([CH3:47])[CH3:46])(=[O:44])=[O:43])=[CH:38][CH:37]=2)[N:31]=1)#[CH:29].CCN(CC)CC>CN(C=O)C.CCOC(C)=O.O>[CH:45]([S:42]([C:39]1[CH:38]=[CH:37][C:36]([C:32]2[N:31]=[C:30]([C:28]3[O:9][N:10]=[C:11]([C:12]4[CH:13]=[CH:14][C:15]([CH2:16][N:17]([CH3:25])[C:18](=[O:24])[O:19][C:20]([CH3:21])([CH3:22])[CH3:23])=[CH:26][CH:27]=4)[CH:29]=3)[CH:35]=[N:34][CH:33]=2)=[CH:41][CH:40]=1)(=[O:43])=[O:44])([CH3:47])[CH3:46]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 31398ChlorosuccinimideHCID 866651492-Ethynyl-6-(4-(isopropylsulfonyl)phenyl)pyrazineHCID 86690358Tert-butyl 4-((hydroxyimino)methyl)benzyl(methyl)carbamate

Product 1

HCID 67480464tert-butyl N-[[4-[5-[6-(4-isopropylsulfonylphenyl)pyrazin-2-yl]isoxazol-3-yl]phenyl]methyl]-N-methyl-carbamate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

NCS (34.97 mg, 0.2619 mmol) was added to a solution of tert-butyl 4-((hydroxyimino)methyl)benzyl(methyl)carbamate (62.93 mg, 0.2381 mmol) in DMF (1 mL) and the mixture heated at 65° C. for 15 minutes. The reaction mixture was cooled to ambient temperature and 2-ethynyl-6-(4-isopropylsulfonylphenyl)pyrazine (75 mg, 0.2619 mmol) and DMF (2 mL) were added followed by the dropwise addition of Et3N (28.91 mg, 39.82 μL, 0.2857 mmol). The mixture was stirred at ambient temperature for 45 minutes then heated to 65° C. for 1 hour. The mixture was cooled to ambient temperature and diluted with EtOAc and water and the layers separated. The aqueous layer was extracted with EtOAc (×2) and the combined organic extracts washed with water (×3), brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography (ISCO Companion™, 12 g column, eluting with 0 to 40% EtOAc/Petroleum Ether) to give the sub-title product as a yellow solid. 1H NMR (400.0 MHz, DMSO) d H NMR (400.0 MHz, DMSO) d 9.53 (s, 1H), 9.32 (s, 1H), 8.58 (d, 2H), 8.09 (s, 1H), 8.06 (d, 2H), 8.01 (d, 2H), 7.42 (d, 2H), 4.47 (s, 2H), 3.55 (sept, 1H), 2.82 (s, 3H), 1.46-1.41 (2×s, 9H) and 1.21 (d, 6H) ppm; MS (ES+) 493.2

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. temperaturethen heated to 65° C. for 1 hour
  3. temperatureThe mixture was cooled to ambient temperature
  4. customthe layers separated
  5. extractionThe aqueous layer was extracted with EtOAc (×2)
  6. washthe combined organic extracts washed with water (×3), brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by column chromatography (ISCO Companion™, 12 g column, eluting with 0 to 40% EtOAc/Petroleum Ether)

Sources & evidence

ORD record
ord-d36ce2cc55ad4198831ee623478d2b0c
Source dataset
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09334244B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes