Acetyl chloride → HCID 86675915, compound

HRID 572659Notes

Reaction equation

HRID 572659 reaction equation
[NH2:1][CH2:2][C@@H:3]1[CH2:8][O:7][C@@H:6]([C@H:9]2[O:13][N:12]=[C:11]([C:14]3[N:19]=[C:18]([CH3:20])[N:17]=[C:16]([C:21]([NH:23][CH2:24][C:25]4[CH:30]=[CH:29][C:28]([F:31])=[C:27]([O:32][CH3:33])[CH:26]=4)=[O:22])[CH:15]=3)[CH2:10]2)[CH2:5][O:4]1.[C:34](Cl)(=[O:36])[CH3:35]>C(Cl)Cl>[C:34]([NH:1][CH2:2][C@@H:3]1[CH2:8][O:7][C@@H:6]([C@H:9]2[O:13][N:12]=[C:11]([C:14]3[N:19]=[C:18]([CH3:20])[N:17]=[C:16]([C:21]([NH:23][CH2:24][C:25]4[CH:30]=[CH:29][C:28]([F:31])=[C:27]([O:32][CH3:33])[CH:26]=4)=[O:22])[CH:15]=3)[CH2:10]2)[CH2:5][O:4]1)(=[O:36])[CH3:35]

Participants

4

Reactant 2

HCID 6367Acetyl chlorideHCID 86675916HCID 86675916, compound

Product 1

HCID 86675915HCID 86675915, compoundYield 74.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of 6-((S)-5-((2R,5R)-5-(aminomethyl)-1,4-dioxan-2-yl)-4,5-dihydroisoxazol-3-yl)-N-(4-fluoro-3-methoxybenzyl)-2-methylpyrimidine-4-carboxamide (0.08 g, 0.174 mmol, Preparation #J.1) in DCM (5 mL) at 0° C., was added TEA (0.073 mL, 0.522 mmol, Spectrochem) followed by acetyl chloride (0.015 mL, 0.209 mmol, Spectrochem). The reaction mixture was stirred for 30 min, was diluted with DCM (30 mL) and washed with water (2×20 mL). The organic layer dried over sodium sulphate and concentrated under reduced pressure. The resulting crude material was purified by preparative TLC eluting with 60% EtOAc in hexane to afford 6-((S)-5-((2R,5R)-5-(acetamidomethyl)-1,4-dioxan-2-yl)-4,5-dihydroisoxazol-3-yl)-N-(4-fluoro-3-methoxybenzyl)-2-methylpyrimidine-4-carboxamide 0.065 g (74%); 1H NMR (400 MHz, DMSO): δ 9.50 (t, J=5.6 Hz, 1H), 8.13 (s, 1H), 7.93 (t, J=5.6 Hz, 1H), 7.17-7.11 (m, 2H), 6.89-6.81 (m, 1H), 4.81-4.75 (m, 1H), 4.48 (d, J=6.4 Hz, 2H), 3.88-3.86 (m, 1H), 3.81 (s, 3H), 3.78-3.63 (m, 2H), 3.46-3.36 (m, 4H), 3.32-3.22 (m, 2H), 3.08-3.00 (m, 2H) 2.75 (s, 3H), 1.79 (s, 3H); LC/MS (Table 1, Method e) Rt=2.69 min; MS: m/z 502 (m+H)+.

Workup

  1. washwashed with water (2×20 mL)
  2. dry with materialThe organic layer dried over sodium sulphate
  3. concentrationconcentrated under reduced pressure
  4. customThe resulting crude material was purified by preparative TLC
  5. washeluting with 60% EtOAc in hexane

Sources & evidence

ORD record
ord-0941d47f7c1b488e8571b55437493f84
Source dataset
uspto-grants-2015_05
Patent number
US09029409B2

Reaction notes

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