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

HRID 2385951Notes

Reaction equation

HRID 2385951 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)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)[O:55][C:37]2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[CH3:76][S:77]([CH2:80][CH2:81][NH2:82])(=[O:79])=[O:78].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:37]([NH:82][CH2:81][CH2:80][S:77]([CH3:76])(=[O:79])=[O:78])=[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 17749886Ethanamine, 2-(methylsulfonyl)-, hydrochloride (1:1)HCID 67050579HCID 67050579, compound

Product 1

HCID 58204176N2-(2-chloro-5-((S)-2-hydroxypropylcarbamoyl)phenyl)-N2-methyl-N8-(2-(methylsulfonyl)ethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamideYield 423.9%

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 (400 mg, 0.73 mmol), Pd(OAc)2 (8 mg, 0.037 mmol), Xantphos (42 mg, 0.073 mmol), MeSO2(CH2)2NH2.HCl (175 mg, 1.095 mmol) and Na2CO3 (232 mg, 2.19 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, the crude product was purified by pre-TLC (eluted by DCM: MeOH=10:1) to give 438 (191.9 mg, yield 42%). 1H NMR (DMSO-d6, 400 MHz): δ8.74 (t, J=5.2 Hz, 1H, NH), 8.62 (t, J=5.2 Hz, 1H, NH), 8.12-7.44 (m, 6H, ArH), 6.61 (s, 1H, ═CH), 4.77 (d, J=4.8 Hz, 1H, OH), 4.20 (br s, 2H, CH2), 3.80-3.75 (m, 1H, CH), 3.67-2.98 (m, 14H, CH3, CH2), 1.05 (t, J=6.0 Hz, 3H, CH3). LC-MS: (ESI, m/z)=620 [M+H]+

Workup

  1. filtrationThen it was filtrated
  2. concentrationconcentrated
  3. customthe crude product was purified by pre-TLC (eluted by DCM: MeOH=10:1)

Sources & evidence

ORD record
ord-04356c710bbd4b48ae6cd8b1054897ee
Source dataset
uspto-grants-2012_09
Patent number
US08263633B2

Reaction notes

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