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

HRID 1190587Notes

Reaction equation

HRID 1190587 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])[N:26]([CH2:28][CH2:29][OH:30])[CH3:27])[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.CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:32][C:20]1[CH:21]=[CH:22][C:23]([C:25](=[O:31])[N:26]([CH2:28][CH2:29][OH:30])[CH3:27])=[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

7

Reactant 4

HCID 10340Sodium CarbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 6364545Methylamine hydrochlorideHCID 58204024HCID 58204024, compound

Product 1

HCID 58204261N2-(2-chloro-5-((2-hydroxyethyl)(methyl)carbamoyl)phenyl)-N2,N8-dimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamideYield 217.3%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A suspension of 8-bromo-N-(2-chloro-5-((2-hydroxyethyl)(methyl)carbamoyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide (400 mg, 0.76 mmol), Pd(OAc)2 (10 mg, 0.045 mmol), Xantphos (44 mg, 0.076 mmol), MeNH2.HCl (77 mg, 1.14 mmol) and Na2CO3 (242 mg, 2.28 mmol) in toluene (5 mL) was heated at 80° C. under atmosphere of CO from balloon overnight. Then it was filtrated and concentrated, the crude product was purified by column (EtOAc: MeOH=10:1) to afford 383 (87.2 mg, yield: 22%). 1HNMR (DMSO-d6, 400 MHz): δ8.45 (d, J=4.4 Hz, 1H), 7.72-7.43 (m, 6H), 6.73 (s, 1H), 4.89-4.76 (m, 1H), 4.20-4.04 (m, 2H), 3.60-2.66 (m, 15H). LC-MS: (ESI, m/z)=528 [M+H]+

Workup

  1. filtrationThen it was filtrated
  2. concentrationconcentrated
  3. customthe crude product was purified by column (EtOAc: MeOH=10:1)

Sources & evidence

ORD record
ord-1aad6eac2579452593bce9070554bb91
Source dataset
uspto-grants-2014_03
Patent number
US08673952B2

Reaction notes

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