(1S)-2-Chloro-1-methyl-2-oxoethyl acetate → HCID 86675918, compound

HRID 572663Notes

Reaction equation

HRID 572663 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]([O:37][C@@H:38]([CH3:42])[C:39](Cl)=[O:40])(=[O:36])[CH3:35]>C(Cl)Cl>[C:34]([O:37][C@@H:38]([CH3:42])[C:39]([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[CH:15]=[C:16]([C:21](=[O:22])[NH:23][CH2:24][C:25]4[CH:30]=[CH:29][C:28]([F:31])=[C:27]([O:32][CH3:33])[CH:26]=4)[N:17]=[C:18]([CH3:20])[N:19]=3)[CH2:10]2)[CH2:5][O:4]1)=[O:40])(=[O:36])[CH3:35]

Participants

4

Reactant 2

HCID 11094804(1S)-2-Chloro-1-methyl-2-oxoethyl acetateHCID 86675916HCID 86675916, compound

Product 1

HCID 86675918HCID 86675918, compoundYield 58.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

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 (0.15 g, 0.326 mmol, Preparation #J.1) in DCM (3 mL) at 0° C., was added TEA (0.100 mL, 0.718 mmol) followed by (S)-(−)-2-acetoxypropionylchloride (0.045 mL, 0.359 mmol, Spectrochem). The reaction mixture was stirred for 30 min. at the same temperature and was quenched with water (10 mL). The product was extracted with DCM (2×10 mL). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure. The resulting crude was purified using silica gel column chromatography by eluting with 70% EtOAc in hexane. The relevant fractions containing compound were combined and concentrated to afford (S)-1-(((2R,5R)-5-((S)-3-(6-(4-fluoro-3-methoxybenzylcarbamoyl)-2-methylpyrimidin-4-yl)-4,5-dihydroisoxazol-5-yl)-1,4-dioxan-2-yl)methylamino)-1-oxopropan-2-yl acetate 0.11 g (58%); 1H NMR (400 MHz, DMSO): δ 9.48 (t, J=6.4 Hz, 1H), 8.13 (s, 1H), 7.17-7.11 (m, 2H), 6.89-6.86 (m, 1H), 4.87-4.85 (m, 1H), 4.79-4.78 (m, 1H), 4.48 (d, J=6.4 Hz, 2H), 3.88-3.85 (m, 1H), 3.81 (s, 3H), 3.74-3.63 (m, 2H), 3.49-3.37 (m, 4H), 3.26-3.21 (m, 2H), 3.09-3.07 (m, 2H), 2.75 (s, 3H), 2.04 (s, 3H), 1.30 (d, J=6.8 Hz, 3H); LC/MS) (Table 1, method c) Rt=3.12 min; MS: m/z 574 (m+H)+.

Workup

  1. customwas quenched with water (10 mL)
  2. extractionThe product was extracted with DCM (2×10 mL)
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting crude was purified
  6. washby eluting with 70% EtOAc in hexane
  7. additionThe relevant fractions containing compound
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-d672b7cb7d914524b3211ed062f02fd3
Source dataset
uspto-grants-2015_05
Patent number
US09029409B2

Reaction notes

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