Cesium carbonate → HCID 86677519, compound

HRID 1500797Notes

Reaction equation

HRID 1500797 reaction equation
Cl[C:2]1[N:7]=[C:6]2[N:8]([CH:11]3[CH2:16][CH2:15][CH2:14][CH2:13][O:12]3)[N:9]=[CH:10][C:5]2=[C:4]([C:17]2[CH:18]=[C:19]([NH:23][C:24](=[O:27])[CH:25]=[CH2:26])[CH:20]=[CH:21][CH:22]=2)[N:3]=1.[O:28]1[CH2:33][CH2:32][N:31]([C:34]2[CH:40]=[CH:39][C:37]([NH2:38])=[CH:36][CH:35]=2)[CH2:30][CH2:29]1.C([O-])([O-])=O.[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[O:28]1[CH2:29][CH2:30][N:31]([C:34]2[CH:35]=[CH:36][C:37]([NH:38][C:2]3[N:7]=[C:6]4[N:8]([CH:11]5[CH2:16][CH2:15][CH2:14][CH2:13][O:12]5)[N:9]=[CH:10][C:5]4=[C:4]([C:17]4[CH:18]=[C:19]([NH:23][C:24](=[O:27])[CH:25]=[CH2:26])[CH:20]=[CH:21][CH:22]=4)[N:3]=3)=[CH:39][CH:40]=2)[CH2:32][CH2:33]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 75655Benzenamine, 4-(4-morpholinyl)-HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86677518N-(3-(6-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)phenyl)acrylamide

Product 1

HCID 86677519HCID 86677519, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
200 °C

Procedure

N-(3-(6-Chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)phenyl)acrylamide (50 mg, 0.130 mmol), 4-morpholinoaniline (23.22 mg, 0.130 mmol) and Cs2CO3 (42.4 mg, 0.130 mmol) were dissolved in toluene (4.5 mL) in a sealable microwave compatible reaction tube, and then Pd2(dba)3 (2.386 mg, 2.61 μmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (3.01 mg, 5.21 μmol) were added. The reaction tube was sealed and the reaction heated under microwave irradiation (30 min, 200° C., 3 atm). After completion of the reaction, the solvent was removed by vacuum and product was purified by flash column chromatography. 1H NMR (400 MHz, CD3OD): δ 8.64 (s, 1H), 8.28 (s, 1H), 7.93 (d, 1H, J=8.0 Hz), 7.72 (m, 3H), 7.50 (m, 1H), 6.96 (m, 2H), 6.43 (m, 2H), 5.90 (d, 1H, J=8.4 Hz), 5.80 (dd, 1H, J=2.8 and 8.8 Hz), 4.09 (m, 1H), 3.83 (m, 4H), 3.75 (m, 1H), 3.09 (m, 4H), 3.05 (m, 1H), 2.66 (m, 1H), 2.12 (m, 1H), 1.96 (m, 1H), 1.83-1.73 (m, 2H); ESI-MS: [M+H]+.

Workup

  1. customThe reaction tube was sealed
  2. customAfter completion of the reaction
  3. customthe solvent was removed by vacuum and product
  4. customwas purified by flash column chromatography

Sources & evidence

ORD record
ord-b095ec148d7b4084aa3b79b471f90d00
Source dataset
uspto-grants-2015_12
Patent number
US09206176B2

Reaction notes

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