Ethyl isocyanate → HCID 71466166, compound

HRID 572670Notes

Reaction equation

HRID 572670 reaction equation
Cl.[F:2][C:3]1[CH:30]=[CH:29][C:6]([CH2:7][NH:8][C:9]([C:11]2[CH:16]=[C:15]([C:17]3[CH2:21][CH:20]([CH:22]4[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]4)[O:19][N:18]=3)[N:14]=[C:13]([CH3:28])[N:12]=2)=[O:10])=[CH:5][C:4]=1[O:31][CH3:32].[CH2:33]([N:35]=[C:36]=[O:37])[CH3:34]>C(Cl)Cl.O>[CH2:33]([NH:35][C:36]([N:25]1[CH2:24][CH2:23][CH:22]([CH:20]2[O:19][N:18]=[C:17]([C:15]3[N:14]=[C:13]([CH3:28])[N:12]=[C:11]([C:9]([NH:8][CH2:7][C:6]4[CH:29]=[CH:30][C:3]([F:2])=[C:4]([O:31][CH3:32])[CH:5]=4)=[O:10])[CH:16]=3)[CH2:21]2)[CH2:27][CH2:26]1)=[O:37])[CH3:34]

Participants

5

Reactant 2

HCID 8022Ethyl isocyanateHCID 71466164HCID 71466164, compound

Product 1

HCID 71466166HCID 71466166, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a cold solution of N-(4-fluoro-3-methoxybenzyl)-2-methyl-6-(5-(piperidin-4-yl)-4,5-dihydroisoxazol-3-yl)pyrimidine-4-carboxamide hydrochloride (0.10 g, 0.21 mmol, Preparation #K.1) and TEA (0.065 g, 0.64 mmol, Sd Fine Chem) in DCM (10 mL) was added ethyl isocyanate (0.018 g, 0.25 mmol, Lancaster). The reaction mixture was slowly warmed to RT and stirred for about 2 h. The reaction mixture was diluted with water (20 mL) and the product extracted with DCM (2×20 mL). The combined organic layers were washed with water (1×25 mL) followed by brine (1×50 mL). The organic layer was dried over sodium sulphate and concentrated under reduced pressure. The crude material obtained was purified using silica gel column chromatography eluted in 1% methanol in DCM. Relevant fractions containing the required compound were combined and evaporated to dryness under reduced pressure to afford 6-(5-(1-(ethylcarbamoyl)piperidin-4-yl)-4,5-dihydroisoxazol-3-yl)-N-(4-fluoro-3-methoxybenzyl)-2-methylpyrimidine-4-carboxamide as an off white solid 60 mg (56%): LC/MS (Table 1, Method c) Rt=1.83 min; MS m/z: 499.2 (M+H)+.

Workup

  1. extractionthe product extracted with DCM (2×20 mL)
  2. washThe combined organic layers were washed with water (1×25 mL)
  3. dry with materialThe organic layer was dried over sodium sulphate
  4. concentrationconcentrated under reduced pressure
  5. customThe crude material obtained
  6. customwas purified
  7. washeluted in 1% methanol in DCM
  8. additionRelevant fractions containing the required compound
  9. customevaporated to dryness under reduced pressure

Sources & evidence

ORD record
ord-c80eb283309d45a28419131fdd1b2004
Source dataset
uspto-grants-2015_05
Patent number
US09029409B2

Reaction notes

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