Cesium carbonate → HCID 117772681, compound

HRID 2201534Notes

Reaction equation

HRID 2201534 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:20]=[C:19]([N:21]([CH3:26])[S:22]([CH3:25])(=[O:24])=[O:23])[C:18]([C:27]4[N:32]=[C:31]([C:33]([NH:35][CH2:36][C:37]5[CH:42]=[CH:41][C:40]([F:43])=[CH:39][N:38]=5)=[O:34])[C:30]([OH:44])=[CH:29][CH:28]=4)=[CH:17][C:11]=3[C:12]=2[C:13](=[O:16])[NH:14][CH3:15])=[CH:4][CH:3]=1.[C:45]([O-])([O-])=O.[Cs+].[Cs+].ClCI>CN(C=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[O:9][C:10]3[CH:20]=[C:19]([N:21]([CH3:26])[S:22]([CH3:25])(=[O:24])=[O:23])[C:18]([C:27]4[CH:28]=[CH:29][C:30]5[O:44][CH2:45][N:35]([CH2:36][C:37]6[CH:42]=[CH:41][C:40]([F:43])=[CH:39][N:38]=6)[C:33](=[O:34])[C:31]=5[N:32]=4)=[CH:17][C:11]=3[C:12]=2[C:13]([NH:14][CH3:15])=[O:16])=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 11644ChloroiodomethaneHCID 117771050HCID 117771050, compound

Product 1

HCID 117772681HCID 117772681, compoundYield 63.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 6-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)-N-((5-fluoropyridin-2-yl)methyl)-3-hydroxypicolinamide (30 mg, 0.05 mmol) and Cs2CO3 (47 mg, 0.14 mmol) in DMF (3 mL) at 100° C. was added chloroiodomethane (13 mg, 0.07 mmol) under N2 protection dropwise. The mixture was stirred at 100° C. for 3 h. The mixture was concentrated, diluted with water and extracted with EtOAc. The organic phase was dried over Na2SO4 After concentration, the residue was purified by prep-HPLC to give the product of 2-(4-fluorophenyl)-5-(3-((5-fluoropyridin-2-yl)methyl)-4-oxo-3,4-dihydro-2H-pyrido[2,3-e][1,3]oxazin-6-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (20 mg, yield: 60%). 1H-NMR (CDCl3, 400 MHz) δ 8.33 (s, 1H), 7.90˜7.94 (m, 3H), 7.69 (d, J=8.8 Hz, 1H), 7.56 (s, 1H), 7.40˜7.44 (m, 2H), 7.31˜7.36 (m, 1H), 7.13 (t, J=8.8 Hz, 2H), 6.19 (br s, 1H), 5.43 (s, 2H), 4.82 (s, 2H), 3.15 (s, 3H), 2.92 (d, J=4.8 Hz, 3H), 2.85 (s, 3H). MS (M+H)+: 634.

Workup

  1. concentrationThe mixture was concentrated
  2. additiondiluted with water
  3. extractionextracted with EtOAc
  4. dry with materialThe organic phase was dried over Na2SO4
  5. concentrationAfter concentration
  6. customthe residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-e34832a182154401bbc1b93c65bf41db
Source dataset
uspto-grants-2016_06
Patent number
US09364482B2

Reaction notes

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