Methanesulfonyl chloride → HCID 71466081, compound

HRID 572660Notes

Reaction equation

HRID 572660 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].[CH3:33][S:34](Cl)(=[O:36])=[O:35]>C(Cl)Cl.O>[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[CH2:23][CH2:24][N:25]([S:34]([CH3:33])(=[O:36])=[O:35])[CH2:26][CH2:27]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]

Participants

5

Reactant 2

HCID 31297Methanesulfonyl chlorideHCID 71466164HCID 71466164, compound

Product 1

HCID 71466081HCID 71466081, compoundYield 59.8%

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 (0.1 g, 0.215 mmol, Preparation #K.1) and TEA (0.141 g, 1.4 mmol, Sd Fine Chem) in DCM (10 mL) was added methane sulfonyl chloride (0.032 g, 0.28 mmol, Spectrochem). The reaction mixture was slowly warmed to RT and stirred for about 0.5 h. The reaction mixture was diluted with water (10 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 60% EtOAc-hexane. Relevant fractions containing the required compound were combined and evaporated to dryness under reduced pressure to afford N-(4-fluoro-3-methoxybenzyl)-2-methyl-6-(5-(1-(methylsulfonyl)piperidin-4-yl)-4,5-dihydroisoxazol-3-yl)pyrimidine-4-carboxamide as light pale yellow solid 0.065 g (55%): 1H NMR (400 MHz, DMSO): δ 9.501-9.469 (t, J=6.4 Hz, 1H), 8.144 (s, 1H), 7.179-7.135 (m, 2H), 6.901-6.890 (m, 1H), 4.730-4.692 (m, 1H), 4.483-4.467 (d, J=6.4 Hz, 2H), 3.815 (s, 3H), 3.617-3.587 (d, J=12 Hz, 2H), 3.517-3.489 (m, 2H), 2.848 (s, 3H) 2.755 (s, 3H), 2.699-2.639 (m, 2H), 1.896-1.864 (m, 1H), 1.740-1.711 (m, 2H), 1.323-1.236 (m, 2H). LC/MS (Table 1, Method c) Rt=4.71 min MS m/z: 506 (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 60% EtOAc-hexane
  8. additionRelevant fractions containing the required compound
  9. customevaporated to dryness under reduced pressure

Sources & evidence

ORD record
ord-c5db670f2a3b40a0843a4bda21d4f75a
Source dataset
uspto-grants-2015_05
Patent number
US09029409B2

Reaction notes

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