Triethylamine → HCID 86680964, compound

HRID 331500Notes

Reaction equation

HRID 331500 reaction equation
C(OC([N:8]([C:16]1[C:21]([C:22]#[CH:23])=[N:20][C:19]([C:24]2[CH:29]=[CH:28][N:27]=[C:26]([C:30]([C:33]#[N:34])([CH3:32])[CH3:31])[CH:25]=2)=[CH:18][N:17]=1)C(=O)OC(C)(C)C)=O)(C)(C)C.[Cl:35][CH2:36][C:37]1[CH:46]=[CH:45][C:40]([C:41](Cl)=[N:42][OH:43])=[CH:39][CH:38]=1.CCN(CC)CC>>[NH2:8][C:16]1[N:17]=[CH:18][C:19]([C:24]2[CH:29]=[CH:28][N:27]=[C:26]([C:30]([CH3:31])([CH3:32])[C:33]#[N:34])[CH:25]=2)=[N:20][C:21]=1[C:22]1[O:43][N:42]=[C:41]([C:40]2[CH:45]=[CH:46][C:37]([CH2:36][Cl:35])=[CH:38][CH:39]=2)[CH:23]=1

Participants

4

Reactant 3

HCID 8471Triethylamine2×HCID 766866014-(Chloromethyl)-N-hydroxybenzimidoyl chloride2×HCID 86680965HCID 86680965, compound

Product 1

HCID 86680964HCID 86680964, compound

Procedure

A mixture of tert-butyl N-tert-butoxycarbonyl-N-[5-[2-(1-cyano-1-methyl-ethyl)-4-pyridyl]-3-ethynyl-pyrazin-2-yl]carbamate (300 mg, 0.6472 mmol), 4-(chloromethyl)-N-hydroxybenzimidoyl chloride (158.5 mg, 0.7766 mmol) and Et3N (98.24 mg, 135.3 μL, 0.9708 mmol) were stirred at ambient temperature for 60 hours. A further aliquot of 4-(chloromethyl)-N-hydroxybenzimidoyl chloride (50.0 mg, 0.2450 mmol) and Et3N (36.30 mg, 50.0 μL, 0.3587 mmol) were added and the reaction mixture stirred at ambient temperature for a further 24 hours. The reaction mixture was partitioned between DCM and saturated aqueous NaHCO3 and the layers separated. The aquoeus layer was extracted with DCM (×3) and the combined organic extracts dried (MgSO4), filtered and concentrated in vacuo. The residue was dissolved in DCM (10 mL) and TFA (2 mL) was added. The reaction mixture was stirred at ambient temperature for 1 hour then concentrated in vacuo. The residue was partitioned between DCM and saturated aqueous NaHCO3 and the layers separated. The aquoeus layer was extracted with DCM (×3) and the combined organic extracts dried (MgSO4), filtered and concentrated in vacuo yielding 2-(4-(5-amino-6-(3-(4-(chloromethyl)phenyl)isoxazol-5-yl)pyrazin-2-yl)pyridin-2-yl)-2-methylpropanenitrile as a yellow solid that was used without further purification

Workup

  1. stirringthe reaction mixture stirred at ambient temperature for a further 24 hours
  2. customThe reaction mixture was partitioned between DCM and saturated aqueous NaHCO3
  3. customthe layers separated
  4. extractionThe aquoeus layer was extracted with DCM (×3)
  5. dry with materialthe combined organic extracts dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. dissolutionThe residue was dissolved in DCM (10 mL)
  9. additionTFA (2 mL) was added
  10. stirringThe reaction mixture was stirred at ambient temperature for 1 hour
  11. concentrationthen concentrated in vacuo
  12. customThe residue was partitioned between DCM and saturated aqueous NaHCO3
  13. customthe layers separated
  14. extractionThe aquoeus layer was extracted with DCM (×3)
  15. dry with materialthe combined organic extracts dried (MgSO4)
  16. filtrationfiltered
  17. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-337fe283cd8641fd9c065666e1178013
Source dataset
uspto-grants-2014_11
Patent number
US08877759B2

Reaction notes

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