Potassium Carbonate → HCID 178451815, compound

HRID 1888216Notes

Reaction equation

HRID 1888216 reaction equation
[NH2:1][C:2]([C:4]1[CH:5]=[C:6](Br)[CH:7]=[C:8]2[C:12]=1[NH:11][N:10]=[C:9]2[CH:13]1[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]1)=[O:3].[F:27][C:28]1[CH:29]=[C:30](B(O)O)[CH:31]=[CH:32][CH:33]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:1][C:2]([C:4]1[CH:5]=[C:6]([C:32]2[CH:31]=[CH:30][CH:29]=[C:28]([F:27])[CH:33]=2)[CH:7]=[C:8]2[C:12]=1[NH:11][N:10]=[C:9]2[CH:13]1[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]1)=[O:3]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27339863-Fluorophenylboronic acidHCID 178451813HCID 178451813, compound2×

Product 1

HCID 178451815HCID 178451815, compoundYield 117.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

Following the general procedure of Example 65, a mixture of 1,1-dimethylethyl 4-[7-(aminocarbonyl)-5-bromo-1H-indazol-3-yl]-1-piperidine carboxylate (Intermediate 5) (400 mg, 0.545 mmols), 3-fluorophenyl boronic acid (397 mg, 2.84 mmols), potassium carbonate (782 mg, 5.67 mmol), and Pd(PPh3)4 (218 mg, 0.189 mmol) in dioxane/water (7 mL/1 mL) were reacted. The reaction mixture was concentrated, redissolved in methylene chloride and filtered. The filtrate was concentrated and the residue was purified by using a Gilson semi-preparative HPLC system, eluting with 10% B to 80% B, where A=H2O (0.1% trifluoroacetic acid) and B=CH3CN (0.1% trifluoroacetic acid) pumped at 25 mL/min to give the title compound (280 mg, 68%)

Workup

  1. customwere reacted
  2. concentrationThe reaction mixture was concentrated
  3. dissolutionredissolved in methylene chloride
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated
  6. customthe residue was purified
  7. washeluting with 10% B to 80% B, where A=H2O (0.1% trifluoroacetic acid) and B=CH3CN (0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-71e30ffdbfd44c3a81109184b32b94aa
Source dataset
uspto-grants-2013_08
Patent number
US08501780B2

Reaction notes

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