Water → [6-(4-Methoxymethoxy-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl]-methanol

HRID 2279125Notes

Reaction equation

HRID 2279125 reaction equation
Br[C:2]1[N:7]=[C:6]2[N:8]([CH:12]3[CH2:17][CH2:16][CH2:15][CH2:14][O:13]3)[N:9]=[C:10]([CH3:11])[C:5]2=[C:4]([CH2:18][OH:19])[CH:3]=1.[CH3:20][O:21][CH2:22][O:23][C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1.C(=O)([O-])[O-].[K+].[K+].O>COCCOC.O.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.[Pd].C(OCC)(=O)C>[CH3:20][O:21][CH2:22][O:23][C:24]1[CH:29]=[CH:28][C:27]([C:2]2[N:7]=[C:6]3[N:8]([CH:12]4[CH2:17][CH2:16][CH2:15][CH2:14][O:13]4)[N:9]=[C:10]([CH3:11])[C:5]3=[C:4]([CH2:18][OH:19])[CH:3]=2)=[CH:26][CH:25]=1

Participants

8

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 27625284-(Methoxymethoxy)phenylboronic acid2×HCID 90014303[6-Bromo-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl]-methanol

Product 1

HCID 90013757[6-(4-Methoxymethoxy-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl]-methanolYield 103.2%

Reagents, catalysts & solvents 3

HCID 2734558Bis(tri-tert-butylphosphine)palladium(0)CatalystHCID 8857Ethyl AcetateSolventHCID 18180031Water 1,2-dimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

To a degassed mixture of 141 mg [6-Bromo-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl]-methanol, 95 mg 4-(methoxymethoxy)phenylboronic acid and 65 mg potassium carbonate in DME/water (v/v=2/1, 2.3 mL) at r.t. and under Ar-atmosphere 6 mg palladium(0) bis(tri-tert-butylphosphine) was added and the mixture was stirred at 85° C. for 40 min in a microwave reactor. Then 6 mg palladium(0) bis(tri-tert-butylphosphine) and 95 mg 4-(methoxymethoxy)phenylboronic acid were added and the mixture was stirred at 100° C. for 20 min. To the mixture water and ethyl acetate were added, the phases were separated and the aqueous phase was extracted with ethyl acetate. The combined organic phases were concentrated in vacuo and the residue was triturated with ethyl acetate. The resulting solid was isolated by filtration. 171 mg (100%) of the title compound were obtained.

Workup

  1. additionunder Ar-atmosphere 6 mg palladium(0) bis(tri-tert-butylphosphine) was added
  2. stirringthe mixture was stirred at 100° C. for 20 min
  3. customthe phases were separated
  4. extractionthe aqueous phase was extracted with ethyl acetate
  5. concentrationThe combined organic phases were concentrated in vacuo
  6. customthe residue was triturated with ethyl acetate
  7. customThe resulting solid was isolated by filtration

Sources & evidence

ORD record
ord-37639837d83547b69c2bec0682cd4f89
Source dataset
uspto-grants-2015_09
Patent number
US09133181B2

Reaction notes

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