Sodium Carbonate → HCID 58204175, compound

HRID 1849254Notes

Reaction equation

HRID 1849254 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:20]=[C:21]([CH:37]=[CH:38][C:39]=4[Cl:40])[C:22]([N:24]4[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH2:25]4)=[O:23])[CH3:18])=[O:16])=[CH:14][C:10]=3[CH2:9][CH2:8][O:7][C:6]=2[CH:41]=1.CC1(C)C2[C:64](=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)[O:63]C2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[CH3:84][NH2:85].Cl.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:40][C:39]1[CH:38]=[CH:37][C:21]([C:22]([N:24]2[CH2:25][CH2:26][N:27]([C:30]([O:32][C:33]([CH3:35])([CH3:34])[CH3:36])=[O:31])[CH2:28][CH2:29]2)=[O:23])=[CH:20][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:64](=[O:63])[NH:85][CH3:84])=[CH:41][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 58204000HCID 58204000, compound

Product 1

HCID 58204175HCID 58204175, compoundYield 802.9%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A suspension of tert-butyl 4-(3-(8-bromo-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamido)-4-chlorobenzoyl)piperazine-1-carboxylate (500 mg, 0.76 mmol), Pd(OAc)2 (9 mg, 0.038 mmol), Xantphos (44 mg, 0.076 mmol), MeNH2.HCl (77 mg, 1.14 mmol) and Na2CO3 (242 mg, 2.28 mmol) in toluene (10 mL) was heated at 80° C. under atmosphere of CO from balloon for overnight. Then it was filtrated and concentrated, the crude product was purified by pre-TLC (DCM/MeOH=10:1 as eluted solvent) to give tert-butyl 4-(4-chloro-3-(N-methyl-8-(methylcarbamoyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamido)benzoyl)piperazine-1-carboxylate (390 mg, yield: 80%). 1H NMR (DMSO, 400 MHz): δ7.59-7.26 (m, 8H, ArH, NH), 4.26 (t, J=5.2 Hz, 2H, CH2), 3.57-2.80 (m, 18H, CH2, CH3), 1.47 (s, 9H, CH3)

Workup

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

Sources & evidence

ORD record
ord-7fb1d40b61f943a68608e2aac60b538f
Source dataset
uspto-grants-2015_02
Patent number
US08952043B2

Reaction notes

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