Cesium carbonate → HCID 73388605, compound

HRID 523047Notes

Reaction equation

HRID 523047 reaction equation
Cl[C:2]1[N:3]=[CH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([C:12]1[CH:13]=[N:14][N:15]([CH2:17][C:18]([CH3:21])([OH:20])[CH3:19])[CH:16]=1)=[CH:7][CH:6]=2.[NH2:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]2[N:33]([CH2:34][CH:35]3[CH2:40][CH2:39][N:38](C(OC(C)(C)C)=O)[CH2:37][CH2:36]3)[C:32]([CH3:48])=[N:31][CH:30]=2)=[CH:25][C:24]=1[O:49][CH3:50].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-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.CN(C=O)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]>[CH3:50][O:49][C:24]1[CH:25]=[C:26]([C:29]2[N:33]([CH2:34][CH:35]3[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]3)[C:32]([CH3:48])=[N:31][CH:30]=2)[CH:27]=[CH:28][C:23]=1[NH:22][C:2]1[N:3]=[CH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([C:12]1[CH:13]=[N:14][N:15]([CH2:17][C:18]([CH3:21])([OH:20])[CH3:19])[CH:16]=1)=[CH:7][CH:6]=2

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 89995738HCID 89995738, compoundHCID 118274564HCID 118274564, compound

Product 1

HCID 73388605HCID 73388605, compoundYield 59%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 21735183Dimethylformamide tolueneSolvent

Conditions

Temperature
160 °C

Procedure

A suspension of 1-(4-(3-chloroisoquinolin-6-yl)-1H-pyrazol-1-yl)-2-methylpropan-2-ol (Preparation 22, 15 mg, 0.050 mmol), tert-butyl 4-((5-(4-amino-3-methoxyphenyl)-2-methyl-1H-imidazol-1-yl)methyl)piperidine-1-carboxylate (Preparation 79, 19.9 mg, 0.050 mmol), xantphos (17.3 mg, 0.030 mmol), Pd2(dba)3 (4.6 mg, 0.005 mmol) and Cs2CO3 (130 mg, 0.398 mmol) in toluene/DMF (3/1 mL) was stirred at 160° C. under microwave irradiation for 2 hours. The reaction mixture was filtered, diluted with NaCl solution and extracted with EtOAc. The organic solution was purified by elution through an SCX-2 column using 2M NH3/MeOH followed by preparative HPLC. The residue was dissolved in DCM (6 mL) and cooled to 0° C. TFA (0.2 mL) was added and the reaction stirred at room temperature for 16 hours. The reaction was concentrated in vacuo and purified by elution through an SCX-2 column using 2M NH3/MeOH followed by preparative HPLC to afford the title compound as a yellow oil (2.5 mg, 59%).

Workup

  1. filtrationThe reaction mixture was filtered
  2. additiondiluted with NaCl solution
  3. extractionextracted with EtOAc
  4. customThe organic solution was purified by elution through an SCX-2 column
  5. dissolutionThe residue was dissolved in DCM (6 mL)
  6. temperaturecooled to 0° C
  7. additionTFA (0.2 mL) was added
  8. stirringthe reaction stirred at room temperature for 16 hours
  9. concentrationThe reaction was concentrated in vacuo
  10. custompurified by elution through an SCX-2 column

Sources & evidence

ORD record
ord-d11256e8317d4c9f8012b30770e2ef7a
Source dataset
uspto-grants-2016_05
Patent number
US09334286B2

Reaction notes

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