Potassium Phosphate, Tribasic → HCID 66850735, compound

HRID 1466620Notes

Reaction equation

HRID 1466620 reaction equation
I[C:2]1[N:6]([CH2:7][O:8][CH2:9][CH2:10][Si:11]([CH3:14])([CH3:13])[CH3:12])[N:5]=[CH:4][C:3]=1[NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19].[Cl:23][C:24]1[CH:25]=[C:26](B2OC(C)(C)C(C)(C)O2)[C:27]([O:30][CH3:31])=[N:28][CH:29]=1.COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>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.C(Cl)(Cl)Cl.[Pd].[Pd].C(O)CCC>[Cl:23][C:24]1[CH:25]=[C:26]([C:2]2[N:6]([CH2:7][O:8][CH2:9][CH2:10][Si:11]([CH3:14])([CH3:13])[CH3:12])[N:5]=[CH:4][C:3]=2[NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[C:27]([O:30][CH3:31])=[N:28][CH:29]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 509892825-Chloro-2-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 66851624HCID 66851624, compound

Product 1

HCID 66850735HCID 66850735, compoundYield 52.5%

Reagents, catalysts & solvents 2

HCID 11029508Palladium, tris[mu-[(1,2-eta:4,5-eta)-(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one]]di-, compd. with trichloromethane (1:1)CatalystHCID 2631-ButanolSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of tert-butyl 5-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-ylcarbamate (390.7 mg, 0.8892 mmol), 5-chloro-2-methoxy-pyridine-3-boronic acid pinacol ester (364.0 mg, 1.350 mmol), tris(dibenzylideneacetone)dipalladium(0) chloroform adduct (48.5 mg, 0.0468 mmol), S-Phos (74.2 mg, 0.181 mmol), potassium phosphate (597.1 mg, 2.813 mmol), and 1-butanol (10 mL) was degassed with nitrogen and then stirred at 80° C. for 15 hours. The reaction mixture was diluted in ethyl acetate, washed with water and brine, dried over magnesium sulfate, filtered, and evaporated in vacuo. The crude product was purified via flash chromatography on silica gel (0 to 50% ethyl acetate in heptanes) to yield 212.3 mg (52%) of tert-butyl 5-(5-chloro-2-methoxypyridin-3-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-ylcarbamate. LCMS (ESI) m+H=455.2; 1H NMR (400 MHz, DMSO-d6) δ: 8.53 (s, 1H), 8.33 (s, 1H), 7.79 (d, J=2.6, 1H), 5.22 (s, 2H), 3.85 (s, 3H), 3.35 (t, 2H), 1.38 (s, 9H), 0.70 (t, J=8.1, 2H), −0.10 (s, 9H).

Workup

  1. customwas degassed with nitrogen
  2. additionThe reaction mixture was diluted in ethyl acetate
  3. washwashed with water and brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe crude product was purified via flash chromatography on silica gel (0 to 50% ethyl acetate in heptanes)

Sources & evidence

ORD record
ord-abd75aeae2ee4c2580306d463c86fbbf
Source dataset
uspto-grants-2015_04
Patent number
US08999998B2

Reaction notes

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