Biphenyl → HCID 24986680, compound

HRID 1174553Notes

Reaction equation

HRID 1174553 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]2[S:9][C:10]3[C:11](=[O:20])[NH:12][CH2:13][C:14]([CH3:19])([CH3:18])[CH2:15][C:16]=3[N:17]=2)[CH:5]=[CH:4][N:3]=1.[NH2:21][C:22]1[CH:31]=[CH:30][C:25]([C:26]([NH:28][CH3:29])=[O:27])=[CH:24][CH:23]=1.CC([O-])(C)C.[Na+].C1(C2C=CC=CC=2)C=CC=CC=1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2].O1CCOCC1>[CH3:18][C:14]1([CH3:19])[CH2:13][NH:12][C:11](=[O:20])[C:10]2[S:9][C:8]([C:6]3[CH:5]=[CH:4][N:3]=[C:2]([NH:21][C:22]4[CH:23]=[CH:24][C:25]([C:26]([NH:28][CH3:29])=[O:27])=[CH:30][CH:31]=4)[CH:7]=3)=[N:17][C:16]=2[CH2:15]1

Participants

9

Reactant 5

HCID 7095BiphenylHCID 2355164-Amino-N-methylbenzamideHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 23676156Sodium t-butoxide2×HCID 24986679HCID 24986679, compound

Product 1

HCID 24986680HCID 24986680, compoundYield 19.4%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalyst2×HCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent

Procedure

2-(2-chloropyridin-4-yl)-5,6,7,8-tetrahydro-7,7-dimethylthiazolo[5,4-c]azepin-4-one (70 mg, 1.0 Eq.), 4-amino-N-methyl-benzamide (41 mg, 1.2 Eq.), NaOtBu (61 mg, 2.8 Eq.), Pd(OAc)2 (5 mg, 0.1 Eq.) were suspended/dissolved in dry toluene and degassed (vacuum/N2 cycles×5). 2-Di-tert-butylphosphino)biphenyl (143 mg, 0.2 Eq.) was then added. The resultant mixture was then refluxed overnight. A further portion of NaOtBu (61 mg, 2.8 Eq.), Pd(OAc)2 (5 mg, 0.1 Eq.) and 2-(di-tert-butylphosphino)biphenyl (14 mg, 0.2 Eq.) were added, followed by dry dioxane (0.5 mL). The resultant mixture was refluxed for a further night. The reaction mixture was allowed to cool to RT, partitioned between EtOAc/MeOH (3:1)/NH4Cl, and then extracted into EtOAc/MeOH (3:1) (3×50 mL). The combined organic layers were washed with brine (1×20 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. Purification was achieved using column chromatography (10% MeOH/90% DCM) to obtain the title compound as a bright yellow powder (18.6 mg, 19% yield); 1H NMR (DMSO D6) 1.0 (6H, s), 2.8 (3H, d), 3.0 (2H, s), 3.0 (2H, m), 7.3 (1H, m), 7.5 (1H, s), 7.8 (4H, s), 8.2 (1H, m), 8.3 (2H, m), 9.6 (1H, s); LC/MS M+1 (obs.) 422.20; LC/MS M−1 (obs.) 420.30.

Workup

  1. customdegassed (vacuum/N2 cycles×5)
  2. custompartitioned between EtOAc/MeOH (3:1)/NH4Cl
  3. extractionextracted into EtOAc/MeOH (3:1) (3×50 mL)
  4. washThe combined organic layers were washed with brine (1×20 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification

Sources & evidence

ORD record
ord-ce51e9a856384f7bb8b6c114d332c3ab
Source dataset
uspto-grants-2010_11
Patent number
US07838517B2

Reaction notes

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