Sodium Carbonate → HCID 58204047, compound

HRID 1849351Notes

Reaction equation

HRID 1849351 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[C:11]3[S:12][C:13]([C:15]([N:17]([C:19]4[CH:24]=[C:23]([C:25]([N:27]5[CH2:30][C:29]([F:32])([F:31])[CH2:28]5)=[O:26])[CH:22]=[CH:21][C:20]=4[Cl:33])[CH3:18])=[O:16])=[CH:14][C:10]=3[CH2:9][CH2:8][O:7][C:6]=2[CH:34]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)[O:56][C:38]2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[CH3:77][S:78]([CH2:81][CH2:82][NH2:83])(=[O:80])=[O:79].Cl.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:33][C:20]1[CH:21]=[CH:22][C:23]([C:25]([N:27]2[CH2:28][C:29]([F:31])([F:32])[CH2:30]2)=[O:26])=[CH:24][C:19]=1[N:17]([CH3:18])[C:15]([C:13]1[S:12][C:11]2[C:5]3[CH:4]=[CH:3][C:2]([C:38]([NH:83][CH2:82][CH2:81][S:78]([CH3:77])(=[O:80])=[O:79])=[O:56])=[CH:34][C:6]=3[O:7][CH2:8][CH2:9][C:10]=2[CH:14]=1)=[O:16]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 17749886Ethanamine, 2-(methylsulfonyl)-, hydrochloride (1:1)HCID 58203926HCID 58203926, compound

Product 1

HCID 58204047HCID 58204047, compoundYield 271.6%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A suspension of 8-bromo-N-(2-chloro-5-(3,3-difluoroazetidine-1-carbonyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide (400 mg, 0.70 mmol), Pd(OAc)2 (8 mg, 0.035 mmol), Xantphos (41 mg, 0.070 mmol), MeSO2(CH2)2NH2.HCl (169 mg, 1.06 mmol) and Na2CO3 (224 mg, 2.11 mmol) in toluene (5 mL) and DMF (5 mL) was heated at 80° C. under atmosphere of CO from balloon for 3 h. Then it was filtrated and concentrated, the crude product was purified by flash column chromatography on silica gel (petroleum ether:EtOAc=2:1→1:5 as eluted solvent) to give a white solid which was washed with DCM and dried to give 432 (121.3 mg, yield: 27%). 1H NMR (DMSO-d6, 400 MHz): δ 8.73-6.60 (m, 8H, NH, ArH), 4.75-3.02 (m, 18H). LC-MS: (ESI, m/z)=638 [M+H]+

Workup

  1. filtrationThen it was filtrated
  2. concentrationconcentrated
  3. customthe crude product was purified by flash column chromatography on silica gel (petroleum ether:EtOAc=2:1→1:5 as eluted solvent)
  4. customto give a white solid which
  5. washwas washed with DCM
  6. customdried

Sources & evidence

ORD record
ord-6cc9de6db6374cf480aa1d876a24e573
Source dataset
uspto-grants-2015_02
Patent number
US08952043B2

Reaction notes

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