Acetyl chloride → HCID 71466026, compound

HRID 572658Notes

Reaction equation

HRID 572658 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].[C:33](Cl)(=[O:35])[CH3:34]>C(Cl)Cl.O>[C:33]([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:35])[CH3:34]

Participants

5

Reactant 2

HCID 6367Acetyl chlorideHCID 71466164HCID 71466164, compound

Product 1

HCID 71466026HCID 71466026, 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 (0.1 g, 0.215 mmol, Preparation #K. 1) and TEA (0.2 mL, 1.4 mmol, Sd Fine Chem) in DCM (10 mL) was added acetyl chloride (0.022 g, 0.28 mmol, Spectrochem). The reaction mixture was slowly warmed to RT and stirred for about 10 min. 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 50% EtOAc-hexane. The relevant fractions containing the target compound were combined and evaporated to dryness under reduced pressure to afford 6-(5-(1-acetylpiperidin-4-yl)-4,5-dihydroisoxazol-3-yl)-N-(4-fluoro-3-methoxybenzyl)-2-methylpyrimidine-4-carboxamide as an off white solid 0.05 g (45%): 1H NMR (400 MHz, DMSO): δ 9.469 (t, J=5.6 Hz, 1H), 8.139 (s, 1H), 7.176-7.114 (m, 2H), 6.885 (brs, 1H), 4.679-4.660 (m, 1H), 4.483-4.467 (d, J=6.4 Hz, 2H), 4.436-4.406 (m, 1H), 3.815 (s, 3H), 3.496-3.424 (m, 2H), 3.295-3.239 (m, 2H), 3.194-2.978 (m, 1H), 2.753 (s, 3H), 1.983 (s, 3H), 1.909-1.621 (m, 3H), 1.243-1.189 (m, 2H). LC/MS (Table 1, method c) Rt=1.76 min; MS m/z: 470.1 (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 50% EtOAc-hexane
  8. additionThe relevant fractions containing the target compound
  9. customevaporated to dryness under reduced pressure

Sources & evidence

ORD record
ord-f69172e9779048598db7e5209a5f458a
Source dataset
uspto-grants-2015_05
Patent number
US09029409B2

Reaction notes

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