Tetrahydrofuran → HCID 89473402, compound

HRID 521221Notes

Reaction equation

HRID 521221 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:13]([C:14](=[O:16])[NH2:15])=[CH:12][N:11]([C:17]3([CH2:30][C:31]#[N:32])[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]3)[N:10]=2)=[CH:4][CH:3]=1.[CH3:33][C:34]1[C:38](B2OC(C)(C)C(C)(C)O2)=[C:37]([CH3:48])[O:36][N:35]=1.C(=O)([O-])[O-].[K+].[K+].C1COCC1>CO.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.O>[C:14]([C:13]1[C:9]([NH:8][C:5]2[CH:6]=[CH:7][C:2]([C:38]3[C:34]([CH3:33])=[N:35][O:36][C:37]=3[CH3:48])=[CH:3][CH:4]=2)=[N:10][N:11]([C:17]2([CH2:30][C:31]#[N:32])[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]2)[CH:12]=1)(=[O:16])[NH2:15]

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 27586563,5-Dimethylisoxazole-4-boronic acid pinacol esterHCID 71536246HCID 71536246, compound

Product 1

HCID 89473402HCID 89473402, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolvent

Procedure

tert-Butyl 4-{3-[(4-bromophenyl)amino]-4-carbamoyl-1H pyrazol-1-yl}-4-(cyanomethyl)piperidine-1-carboxylate (Example #2-2) (50 mg, 0.10 mmol), 3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoxazole (22 mg, 0.10 mmol), potassium carbonate (55 mg, 0.40 mmol), and tetrakis(triphenylphosphine)palladium (0) (6 mg, 0.005 mmol) was suspended in 2:1 THF:water (1.2 mL) and heated to 100° C. for 16 hours. The mixture was then cooled to ambient temperature, diluted with MeOH, and filtered through a 0.45 micron nylon syringe filter. The filtrate was concentrated in vacuo and the residue was purified by reverse-phase preparative HPLC (using a gradient elution of 35-70% MeCN/water, with 0.1% v/v TFA modifier). Desired fractions were identified, combined, and lyophilized to afford the title compound, Example #14.

Workup

  1. filtrationfiltered through a 0.45 micron nylon syringe
  2. filtrationfilter
  3. concentrationThe filtrate was concentrated in vacuo
  4. customthe residue was purified by reverse-phase preparative HPLC (
  5. washa gradient elution of 35-70% MeCN/water

Sources & evidence

ORD record
ord-fdac4b59bbaa4677b5b034741943adfe
Source dataset
uspto-grants-2016_05
Patent number
US09328099B2

Reaction notes

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