Ethyl Acetate → 4,5,6,7-Tetrahydro-benzo[b]thiophene-2-carboxylic acid [3-(6-{4-[(2-hydroxy-ethyl)-methyl-carbamoyl]-3-nitro-phenylamino}-4-methyl-5-oxo-4,5-dihydro-pyrazin-2-yl)-2-methyl-phenyl]-amide

HRID 551865

Reaction equation

HRID 551865 reaction equation
Br[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:21]=[CH:20][C:12]([C:13]([N:15]([CH2:17][CH2:18][OH:19])[CH3:16])=[O:14])=[C:11]([N+:22]([O-:24])=[O:23])[CH:10]=2)[C:5](=[O:25])[N:4]([CH3:26])[CH:3]=1.[CH3:27][C:28]1[C:33](B2OC(C)(C)C(C)(C)O2)=[CH:32][CH:31]=[CH:30][C:29]=1[NH:43][C:44]([C:46]1[S:50][C:49]2[CH2:51][CH2:52][CH2:53][CH2:54][C:48]=2[CH:47]=1)=[O:45].C(=O)([O-])[O-].[Na+].[Na+].C(OCC)(=O)C>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:19][CH2:18][CH2:17][N:15]([CH3:16])[C:13]([C:12]1[CH:20]=[CH:21][C:9]([NH:8][C:6]2[C:5](=[O:25])[N:4]([CH3:26])[CH:3]=[C:2]([C:33]3[C:28]([CH3:27])=[C:29]([NH:43][C:44]([C:46]4[S:50][C:49]5[CH2:51][CH2:52][CH2:53][CH2:54][C:48]=5[CH:47]=4)=[O:45])[CH:30]=[CH:31][CH:32]=3)[N:7]=2)=[CH:10][C:11]=1[N+:22]([O-:24])=[O:23])=[O:14]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 587290674-(6-Bromo-4-methyl-3-oxo-3,4-dihydro-pyrazin-2-ylamino)-N-(2-hydroxy-ethyl)-N-methyl-2-nitro-benzamideHCID 58729134N-(2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide

Product 1

HCID 587289644,5,6,7-Tetrahydro-benzo[b]thiophene-2-carboxylic acid [3-(6-{4-[(2-hydroxy-ethyl)-methyl-carbamoyl]-3-nitro-phenylamino}-4-methyl-5-oxo-4,5-dihydro-pyrazin-2-yl)-2-methyl-phenyl]-amideYield 61.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

4-(6-Bromo-4-methyl-3-oxo-3,4-dihydro-pyrazin-2-ylamino)-N-(2-hydroxy-ethyl)-N-methyl-2-nitro-benzamide (4) (250 mg, 0.59 mmol, 1.0 equiv), 4,5,6,7-Tetrahydro-benzo[b]thiophene-2-carboxylic acid[2-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-amide (257 mg, 0.65 mmol) and tetrakis(triphenylphosphine)palladium (68 mg, 0.06 mmol) are dissolved in 1,4-dioxane (2.0 mL) and sodium carbonate (1N, 1.0 mL) and heated in a microwave glass reactor for 6 minutes at 140° C. Once completed the reaction is transferred to a seperatory funnel with ethyl acetate (50 mL) and washed with saturated sodium bicarbonate (1×100 mL), then washed with saturated sodium chloride (1×100 mL) and dried over sodium sulfate. The solution is then filtered and concentrated under reduced pressure. The resulting residue is then triturated with DCM and hexane to give 4,5,6,7-tetrahydro-benzo[b]thiophene-2-carboxylic acid [3-(6-{4-[(2-hydroxy-ethyl)-methyl-carbamoyl]-3-nitro-phenylamino}-4-methyl-5-oxo-4,5-dihydro-pyrazin-2-yl)-2-methyl-phenyl]-amide (5) as a light yellow solid (225 mg).

Workup

  1. washwashed with saturated sodium bicarbonate (1×100 mL)
  2. washwashed with saturated sodium chloride (1×100 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationThe solution is then filtered
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue is then triturated with DCM and hexane

Sources & evidence

ORD record
ord-f547320ad77b46088c98ed57b62307cf
Source dataset
uspto-grants-2011_05
Patent number
US07947835B2

Linked notes

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