Potassium Carbonate → 1,1,1-trifluoro-4-(2-methoxy-5-pyridin-3-ylphenyl)-4-methyl-2-(1H-pyrrolo[2,3-c]pyridin-2-ylmethyl)pentan-2-ol

HRID 400673Notes

Reaction equation

HRID 400673 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([O:28][CH3:29])=[C:6]([C:8]([CH3:27])([CH3:26])[CH2:9][C:10]([CH2:16][C:17]2[NH:25][C:20]3=[CH:21][N:22]=[CH:23][CH:24]=[C:19]3[CH:18]=2)([OH:15])[C:11]([F:14])([F:13])[F:12])[CH:7]=1.B1([C:36]2[CH:41]=[CH:40][CH:39]=[N:38][CH:37]=2)OCCCO1.C(=O)([O-])[O-].[K+].[K+]>COCCOC.CO.CN(C=O)C.C(OCC)(=O)C.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>[F:12][C:11]([F:14])([F:13])[C:10]([CH2:16][C:17]1[NH:25][C:20]2=[CH:21][N:22]=[CH:23][CH:24]=[C:19]2[CH:18]=1)([OH:15])[CH2:9][C:8]([C:6]1[CH:7]=[C:2]([C:36]2[CH:37]=[N:38][CH:39]=[CH:40][CH:41]=2)[CH:3]=[CH:4][C:5]=1[O:28][CH3:29])([CH3:27])[CH3:26]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 41980053-(1,3,2-Dioxaborinan-2-yl)pyridineHCID 469390184-(5-bromo-2-methoxyphenyl)-1,1,1-trifluoro-4-methyl-2-(1H-pyrrolo[2,3-c]pyridin-2-ylmethyl)pentan-2-ol

Product 1

HCID 600264501,1,1-trifluoro-4-(2-methoxy-5-pyridin-3-ylphenyl)-4-methyl-2-(1H-pyrrolo[2,3-c]pyridin-2-ylmethyl)pentan-2-olYield 48%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 86594022DME MeOH DMFSolvent

Procedure

A mixture of 4-(5-bromo-2-methoxyphenyl)-1,1,1-trifluoro-4-methyl-2-(1H-pyrrolo[2,3-c]pyridin-2-ylmethyl)pentan-2-ol (188 mg, 0.4 mmol), pyridine 3-boronic acid 1,3-propanediol cyclic ester (89 mg, 0.6 mmol), potassium carbonate (K2CO3; 166 mg, 1.2 mmol), and Pd(PPh3)4 (46.2 mg, 0.04 mmol) in 3.0 mL of DME-MeOH-DMF (1:1.5:0.5) was microwaved for 20 minutes at 120° C., cooled to room temperature, diluted with 20 mL of ethyl acetate and filtered through diatomaceous earth. The filtrate was washed with 5 mL of 1.0 M aqueous sodium hydroxide solution, water, and brine, dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by silica gel chromatography to yield 90 mg (48% yield) of the title compound as a white foam.

Workup

  1. customwas microwaved for 20 minutes at 120° C.
  2. filtrationfiltered through diatomaceous earth
  3. washThe filtrate was washed with 5 mL of 1.0 M aqueous sodium hydroxide solution, water, and brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-b2319c32d2214ed39b9f0eb83982e198
Source dataset
uspto-grants-2014_06
Patent number
US08741897B2

Reaction notes

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