Potassium Phosphate, Tribasic → HCID 118598677, compound

HRID 1050372Notes

Reaction equation

HRID 1050372 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]2[N:14]=[CH:13][N:12]=[C:11]([NH:15]C(C3CC3)=O)[CH:10]=2)[C:5](=[O:21])[N:4]2[C:22]([C:27]3C=[CH:31][CH:30]=[C:29](F)[CH:28]=3)(C)[NH:23][C:24](=[O:25])[C:3]=12.ClC1C=C(N(CC2C=CC(OC)=CC=2)C2C=CN=CN=2)C(=O)[N:37]2C3(CCCCC3)N(CC3C=CC(OC)=CC=3)C(=O)[C:36]=12.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C(O)(C)(C)C.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:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]2[N:14]=[CH:13][N:12]=[C:11]3[NH:15][N:37]=[CH:36][C:10]=23)[C:5](=[O:21])[N:4]2[C:22]3([NH:23][C:24](=[O:25])[C:3]=12)[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]3

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 118598561HCID 118598561, compoundHCID 118599037HCID 118599037, compound

Product 1

HCID 118598677HCID 118598677, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6386tert-ButanolSolvent

Conditions

Temperature
90 °C

Procedure

To a suspension of 6-bromo-8-chloro-spiro[2H-imidazo[1,5-a]pyridine-3,1′-cyclohexane]-1,5-dione (1, 0.5 g, 1.51 mmol), 1H-pyrazolo[3,4-d]pyrimidin-4-amine (2, 0.2 g, 1.51 mmol) in tert-butanol (20 mL) in a vial, potassium phosphate (0.96 g, 4.54 mmol) was added and the reaction mixture was degassed with argon for 15 min. To this mixture XantPhos (4 mg, 0.08 mmol) and Pd2(dba)3 (7 mg, 0.08 mmol) was added and the reaction mixture was further degassed with argon for 5 min. The reaction mixture was heated at 90° C. for 18 h. TLC showed consumption of starting material, the reaction mixture was filtered over celite bed and washed with dichloromethane followed by concentration of the filtrate. The crude was stirred with methanol (10 mL) and filtered. The resulting solid was further washed with diethyl ether (20 mL) and dried under vacuum to afford 8-chloro-6-(1H-pyrazolo[3,4-d]pyrimidin-4-ylamino)spiro[2H-imidazo[1,5-a]pyridine-3,1′-cyclohexane]-1,5-dione (Cpd. No. 145). Yield: 0.037 g, 6%; MS (ESI) m/z 386.36 [M+1]+; 1H NMR (400 MHz, DMSO-d6) δ 10.39 (s, 1H), 9.55 (s, 1H), 8.91 (s, 1H), 8.61 (s, 2H), 2.97 (m, 2H), 1.76-1.56 (m, 7H), 1.23 (m, 1H).

Workup

  1. additionwas added
  2. customthe reaction mixture was degassed with argon for 15 min
  3. customthe reaction mixture was further degassed with argon for 5 min
  4. customconsumption of starting material
  5. filtrationthe reaction mixture was filtered over celite bed
  6. washwashed with dichloromethane
  7. filtrationfiltered
  8. washThe resulting solid was further washed with diethyl ether (20 mL)
  9. customdried under vacuum

Sources & evidence

ORD record
ord-7e989afa529a4e36b10b1c3705e58870
Source dataset
uspto-grants-2016_07
Patent number
US09382248B2

Reaction notes

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