Cesium carbonate → HCID 86765077, compound

HRID 2201519Notes

Reaction equation

HRID 2201519 reaction equation
[CH2:1]([NH:8][C:9](=[O:43])[C:10]1[C:15]([OH:16])=[CH:14][CH:13]=[C:12]([C:17]2[C:18]([N:37]([CH3:42])[S:38]([CH3:41])(=[O:40])=[O:39])=[CH:19][C:20]3[O:24][C:23]([C:25]4[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=4)=[C:22]([C:32](=[O:35])[NH:33][CH3:34])[C:21]=3[CH:36]=2)[N:11]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:44]([O-])([O-])=O.[Cs+].[Cs+].ClCI>CN(C=O)C>[CH2:1]([N:8]1[C:9](=[O:43])[C:10]2[N:11]=[C:12]([C:17]3[C:18]([N:37]([CH3:42])[S:38]([CH3:41])(=[O:40])=[O:39])=[CH:19][C:20]4[O:24][C:23]([C:25]5[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=5)=[C:22]([C:32]([NH:33][CH3:34])=[O:35])[C:21]=4[CH:36]=3)[CH:13]=[CH:14][C:15]=2[O:16][CH2:44]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 11644ChloroiodomethaneHCID 117771752HCID 117771752, compound

Product 1

HCID 86765077HCID 86765077, compoundYield 19.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of N-benzyl-6-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)-3-hydroxypicolinamide (100 mg, 0.17 mmol) and Cs2CO3 (117 mg, 0.33 mmol) in DMF (20 mL) was added chloroiodomethane (47 mg, 0.25 mmol) dropwise at 110° C. under N2. The mixture was stirred at 110° C. for 0.5 hour. Then the mixture was concentrated and extracted with EtOAc. The combined organic phase was washed with brine, dried over Na2SO4 and concentrated. The residue was purified by prep-TLC (DCM:CH3OH=20:1) to afford the product of 5-(3-benzyl-4-oxo-3,4-dihydro-2H-pyrido[2,3-e][1,3]oxazin-6-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (20 mg, yield: 19.6%). 1H-NMR (CDCl3, 400 MHz) δ 7.88˜7.90 (m, 3H), 7.72˜7.74 (m, 1H), 7.55 (s, 1H), 7.34˜7.39 (m, 5H), 7.25˜7.28 (m, 1H), 7.14 (t, J=7.2 Hz, 2H), 6.87 (br s, 1H), 5.19 (s, 2H), 4.76 (s, 2H), 3.14 (s, 3H), 2.93˜2.94 (m, 6H). MS (M+H)+: 615.

Workup

  1. concentrationThen the mixture was concentrated
  2. extractionextracted with EtOAc
  3. washThe combined organic phase was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified by prep-TLC (DCM:CH3OH=20:1)

Sources & evidence

ORD record
ord-e7546df9f658414c8d556622cae02f83
Source dataset
uspto-grants-2016_06
Patent number
US09364482B2

Reaction notes

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