N-bromobutanimide → HCID 90409730, compound

HRID 589112Notes

Reaction equation

HRID 589112 reaction equation
[CH3:1][C:2]1[C:6]([C:7]2[C:16]3[O:15][CH2:14][C@H:13]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=4)[N:12]4[C:23](=[O:25])[NH:24][C:10]([C:11]=34)=[CH:9][CH:8]=2)=[C:5]([CH3:26])[O:4][N:3]=1.[Br:27]N1C(=O)CCC1=O>O1CCCC1.C(OCC)(=O)C>[Br:27][C:9]1[CH:8]=[C:7]([C:6]2[C:2]([CH3:1])=[N:3][O:4][C:5]=2[CH3:26])[C:16]2[O:15][CH2:14][C@H:13]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=3)[N:12]3[C:23](=[O:25])[NH:24][C:10]=1[C:11]=23

Participants

5

Reactant 2

HCID 67184N-bromobutanimide2×HCID 90410660INCB-54329

Product 1

HCID 90409730HCID 90409730, compoundYield 98%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (4S)-7-(3,5-dimethylisoxazol-4-yl)-4-pyridin-2-yl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazin-2(1H)-one (2.50 g, 7.18 mmol) in tetrahydrofuran (47 mL) was treated with N-bromosuccinimide (1.40 g, 7.89 mmol) and stirred at room temperature for 1 h, at which time the reaction mixture was treated with additional N-bromosuccinimide (0.70 g, 3.93 mmol) and stirred at 45° C. for 3 h. The reaction mixture was diluted with ethyl acetate and washed with water and brine, dried over magnesium sulfate, filtered, and concentrated to give the crude product. Purification by flash column chromatography (50% ethyl acetate/hexanes to 100% ethyl acetate) gave the desired product (3.0 g, 98%) as a single enantiomer. LCMS calculated for C19H16BrN4O3 (M+H)+: m/z=427.1, 429.1. found: 426.8, 428.8.

Workup

  1. stirringstirred at 45° C. for 3 h
  2. washwashed with water and brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give the crude product
  7. customPurification by flash column chromatography (50% ethyl acetate/hexanes to 100% ethyl acetate)

Sources & evidence

ORD record
ord-f00b10c5eeab401aa6b8503b3f6243be
Source dataset
uspto-grants-2016_01
Patent number
US09227985B2

Reaction notes

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