Sodium Carbonate → HCID 67050548, compound

HRID 708172Notes

Reaction equation

HRID 708172 reaction equation
C([O:4][CH2:5][CH2:6][NH:7][C:8](=[O:35])[C:9]1[CH:14]=[CH:13][C:12]([Cl:15])=[C:11]([N:16]([CH3:34])[C:17]([C:19]2[S:33][C:22]3[C:23]4[CH:31]=[CH:30][C:29](Br)=[CH:28][C:24]=4[O:25][CH2:26][CH2:27][C:21]=3[CH:20]=2)=[O:18])[CH:10]=1)(=O)C.CC1(C)C2[C:58](=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)[O:57]C2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[CH3:78][NH2:79].Cl.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:15][C:12]1[CH:13]=[CH:14][C:9]([C:8](=[O:35])[NH:7][CH2:6][CH2:5][OH:4])=[CH:10][C:11]=1[N:16]([CH3:34])[C:17]([C:19]1[S:33][C:22]2[C:23]3[CH:31]=[CH:30][C:29]([C:58]([NH:79][CH3:78])=[O:57])=[CH:28][C:24]=3[O:25][CH2:26][CH2:27][C:21]=2[CH:20]=1)=[O:18]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 6364545Methylamine hydrochlorideHCID 67050629HCID 67050629, compound

Product 1

HCID 67050548HCID 67050548, compoundYield 204.7%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A suspension of 2-(3-(8-bromo-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamido)-4-chlorobenzamido)ethyl acetate (400 mg, 0.69 mmol), Pd(OAc)2 (10 mg, 0.045 mmol), Xantphos (40 mg, 0.069 mmol), MeNH2.HCl (70 mg, 1.04 mmol) and Na2CO3 (219 mg, 2.07 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 dissolved in 10 mL of THF/H2O=1:1. 0.14 g of NaOH was added. The mixture was stirred at room temperature for overnight. The mixture was extracted by DCM and purified by column (EtOAc:MeOH=10:1) to afford 431 (72.6 mg, yield: 20%)1H NMR (DMSO-d6, 400 MHz): δ8.62 (t, J=5.6 Hz, 1H), 8.41 (d, J=4.8 Hz, 1H), 8.07 (s, 1H), 7.95 (d, J=7.6 Hz, 1H), 7.74 (d, J=8.4 Hz, 1H), 7.46 (s, 2H), 7.39 (s, 1H), 6.58 (s, 1H), 4.73 (t, J=5.6 Hz, 1H), 4.16 (s, 2H), 3.50 (dd, J=6.0, 10.0 Hz, 2H), 3.31-3.27 (m, 5H), 2.94 (s, 2H), 2.72 (d, J=4.4 Hz, 3H). LC-MS: (ESI, m/z)=514 [M+H]+

Workup

  1. filtrationThen it was filtrated
  2. concentrationconcentrated
  3. dissolutionthe crude product was dissolved in 10 mL of THF/H2O=1:1
  4. addition0.14 g of NaOH was added
  5. extractionThe mixture was extracted by DCM
  6. custompurified by column (EtOAc:MeOH=10:1)

Sources & evidence

ORD record
ord-38adaed9c0094130828215e1c8303e81
Source dataset
uspto-grants-2015_11
Patent number
US09175009B2

Reaction notes

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