Pyridine → HCID 57330624, compound

HRID 1754351Notes

Reaction equation

HRID 1754351 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([F:11])[C:3]=1[C:4](Cl)=[O:5].[NH2:12][C:13]1[N:14]=[CH:15][C:16]([C:19]2[CH:20]=[C:21]([C:29]3[C:33](=[O:34])[C:32]([CH3:36])([CH3:35])[O:31][N:30]=3)[CH:22]=[CH:23][C:24]=2[C:25]([CH3:28])([CH3:27])[CH3:26])=[N:17][CH:18]=1.N1C=CC=CC=1>C(Cl)Cl>[C:25]([C:24]1[CH:23]=[CH:22][C:21]([C:29]2[C:33](=[O:34])[C:32]([CH3:36])([CH3:35])[O:31][N:30]=2)=[CH:20][C:19]=1[C:16]1[N:17]=[CH:18][C:13]([NH:12][C:4](=[O:5])[C:3]2[C:2]([F:1])=[CH:10][CH:9]=[CH:8][C:7]=2[F:11])=[N:14][CH:15]=1)([CH3:26])([CH3:27])[CH3:28]

Participants

5

Reactant 3

HCID 1049PyridineHCID 874382,6-Difluorobenzoyl chlorideHCID 67518050HCID 67518050, compound

Product 1

HCID 57330624HCID 57330624, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

To a 0° C. cooled and stirred, solution of 2,6-difluorobenzoyl chloride (0.083 mL, 0.66 mmol, 1.5 eq) in DCM (200 mL) was added drop wise a solution of 3-(3-(5-aminopyrazin-2-yl)-4-(tert-butyl)phenyl)-5,5-dimethylisoxazol-4(5H)-one, Intermediate 4b, (150 mg, 0.44 mmol, 1.0 eq) in DCM (50 mL) followed by pyridine (0.053 mL, 0.66 mmol, 1.5 eq). The resulting mixture was stirred at room temperature for 2 h. The reaction was diluted with DCM (100 mL), and washed with 10% hydrochloric acid (100 mL), dried (Na2SO4) and filtered. The filtrate was concentrated under vacuum and the crude product was purified by flash column chromatography (silica gel, 10% ethyl acetate in hexane) to afford 40 mg of the title product as a white solid. 1HNMR (400 MHz, CDCl3) δ 9.72 (s, 1H), 8.55 (s, 1H, D2O exchangeable), 8.28 (s, 1H), 8.14 (dd, J=9.0, 2.5 Hz, 1H), 7.86 (s, 1H), 7.70 (d, J=8.5 Hz, 1H), 7.52-7.45 (m, 1H), 7.07 (t, J=8.5 Hz, 2H), 1.43 (s, 6H), 1.23 (s, 9H); ESI-MS (m/z) 479 (MH)+.

Workup

  1. stirringThe resulting mixture was stirred at room temperature for 2 h
  2. washwashed with 10% hydrochloric acid (100 mL)
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under vacuum
  6. customthe crude product was purified by flash column chromatography (silica gel, 10% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-1275bdb185444776bfc1addc6ce23640
Source dataset
uspto-grants-2015_10
Patent number
US09169242B2

Reaction notes

Loading…