Sodium Carbonate → HCID 58203693, compound
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)C2[C:57](=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)[O:56]C2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[CH3:77][NH2:78].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:33][C:20]1[CH:21]=[CH:22][C:23]([C:25]([N:27]2[CH2:30][C:29]([F:32])([F:31])[CH2:28]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:57]([NH:78][CH3:77])=[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
Product 1
Reagents, catalysts & solvents 3
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), MeNH2.HCl (71 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 4 h, and then filtered and concentrated. The crude product was purified by pre-HPLC to give 448 (121.4 mg, yield 32%). 1H NMR (DMSO, 400 MHz): δ8.45 (m, 1H, NH), 7.98-7.44 (m, 6H, ArH), 6.60 (s, 1H, ═CH), 4.75 (brs, 2H, CH2), 4.48 (br s, 2H, CH2), 4.20 (s, 2H, CH2), 3.30 (s, 3H, CH3), 2.99 (s, 2H, CH2), 2.75 (d, J=4.4 Hz, 3H, CH3). LC-MS: (ESI, m/z)=546 [M+H]+
Workup
- filtrationfiltered
- concentrationconcentrated
- customThe crude product was purified by pre-HPLC
Sources & evidence
- ORD record
- ord-482b2197a7a740e9a415cf6b674e1576
- Source dataset
- uspto-grants-2015_11
- Patent number
- US09175009B2
Reaction notes
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