Potassium Phosphate, Tribasic → HCID 24986679, compound

HRID 1946948Notes

Reaction equation

HRID 1946948 reaction equation
Br[C:2]1[S:3][C:4]2[C:5](=O)[NH:6][C:7](C)(C)C[CH2:9][C:10]=2[N:11]=1.[Cl:15][C:16]1[CH:21]=[C:20](B(O)O)[CH:19]=[CH:18][N:17]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH:33]1(P(C2CCCCC2)C2CCCCC2)CCCCC1.[OH2:52].O1[CH2:58][CH2:57]OCC1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:15][C:16]1[CH:21]=[C:20]([C:2]2[S:3][C:4]3[C:5](=[O:52])[NH:6][CH2:7][C:57]([CH3:58])([CH3:33])[CH2:9][C:10]=3[N:11]=2)[CH:19]=[CH:18][N:17]=1

Participants

7

Reactant 5

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 51515952-Chloropyridine-4-boronic acidHCID 218864351,4-Dioxane--water (1/1)HCID 67422862HCID 67422862, compound

Product 1

HCID 24986679HCID 24986679, compound

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Procedure

2-bromo-5,6,7,8-tetrahydro-6,6-dimethyl thiazolo[5,4-c]azepin-4-one (200 mg, 1.0 Eq.), 2-chloropyridine-4-boronic acid (126 mg, 1.1 Eq.), Pd2(DBA)3 (27 mg, 0.04 Eq.), K3PO4 (341 mg mg, 2.2 Eq.), were suspended/dissolved in H2O/dioxane (0.5 mL/2 5 mL) and degassed (vacuum/N2 cycles×5). Tricyclohexyl phosphine (20 mg, 0.1 Eq.) was then added, and the reaction mixture was 60° C. overnight. The reaction mixture was allowed to cool to RT, partitioned between EtOAc/H2O, and then filtered through celite. The aqueous layer was diluted with sat. Na2CO3 and extracted into EtOAc (3×50 mL). The combined organic layers were washed with brine (1×50 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. Purification was achieved using column chromatography (100% EtOAc), followed by tritration in Et2O. The precipitate was then washed with pentane. The title compound was obtained as a light yellow solid (74.1 mg, 33% yield); 1H NMR (DMSO D6) 1.0 (6H, s), 3.0 (4H, m), 7.9 (1H, m), 8.0 (1H, s), 8.8 (1H, br m), (1H, br m), 9.1 (1H, m); LC/MS M+1; (obs.) 308.1; LC/MS M−1 (obs.) 306.3.

Workup

  1. customdegassed (vacuum/N2 cycles×5)
  2. custompartitioned between EtOAc/H2O
  3. filtrationfiltered through celite
  4. additionThe aqueous layer was diluted with sat. Na2CO3
  5. extractionextracted into EtOAc (3×50 mL)
  6. washThe combined organic layers were washed with brine (1×50 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customPurification
  11. washThe precipitate was then washed with pentane

Sources & evidence

ORD record
ord-5986e2f08c604f34a3cae5781b4a165e
Source dataset
uspto-grants-2013_03
Patent number
US08399458B2

Reaction notes

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