Sodium Carbonate → N2-(2-chloro-5-((S)-2-hydroxypropylcarbamoyl)phenyl)-N2,N8-dimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide

HRID 1849290Notes

Reaction equation

HRID 1849290 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](=[O:31])[NH:26][CH2:27][C@@H:28]([OH:30])[CH3:29])[CH:22]=[CH:21][C:20]=4[Cl:32])[CH3:18])=[O:16])=[CH:14][C:10]=3[CH2:9][CH2:8][O:7][C:6]=2[CH:33]=1.CC1(C)C2[C:56](=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)[O:55]C2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[CH3:76][NH2:77].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:32][C:20]1[CH:21]=[CH:22][C:23]([C:25](=[O:31])[NH:26][CH2:27][C@@H:28]([OH:30])[CH3:29])=[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:56]([NH:77][CH3:76])=[O:55])=[CH:33][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 6364545Methylamine hydrochlorideHCID 67050579HCID 67050579, compound

Product 1

HCID 67050508N2-(2-chloro-5-((S)-2-hydroxypropylcarbamoyl)phenyl)-N2,N8-dimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamideYield 3,009.4%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A suspension of 8-bromo-N-(2-chloro-5-((S)-2-hydroxypropylcarbamoyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide (500 mg, 1.00 mmol), Pd(OAc)2 (11 mg, 0.05 mmol), Xantphos (58 mg, 0.01 mmol), MeNH2.HCl (101 mg, 1.50 mmol) and Na2CO3 (318 mg, 3.00 mmol) in toluene (5 mL) and DMF (5 mL) was heated at 80° C. under atmosphere of CO from balloon overnight. Then it was filtrated and concentrated, diluted with water. The resulting precipitate was washed with water and DCM, dried to give 361 (158.9 mg, yield 30%). 1H NMR (DMSO-d6, 400 MHz): δ8.63-7.43 (m, 8H, NH, ArH), 6.62 (s, 1H, ═CH), 4.77 (d, J=4.0 Hz, 1H, OH), 4.18 (br s, 2H, CH2), 3.78-3.76 (m, 1H, CH), 3.32 (s, 3H, NCH3), 3.24 (br s, 2H, CH2), 2.98 (br s, 2H, CH2), 2.75 (d, J=4.4 Hz, 3H, NCH3)., 1.06 (d, J=6.4 Hz, 3H, CH3). LC-MS: (ESI, m/z)=528 [M+H]+, 550 [M+Na]+

Workup

  1. filtrationThen it was filtrated
  2. concentrationconcentrated
  3. additiondiluted with water
  4. washThe resulting precipitate was washed with water and DCM
  5. customdried

Sources & evidence

ORD record
ord-33dc6afad04847ca8c710ac7ea85b7bc
Source dataset
uspto-grants-2015_02
Patent number
US08952043B2

Reaction notes

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