Biphenyl → HCID 24986680, compound

HRID 1946949Notes

Reaction equation

HRID 1946949 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-c0152beb6f274182ad6738d60721a849
Source dataset
uspto-grants-2013_03
Patent number
US08399458B2

Reaction notes

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