Toluene → (S)-{1-[7-(3,4-difluorophenyl)-3-(4-methoxyphenyl)-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)pyrrolidin-2-yl)methanol

HRID 872092Notes

Reaction equation

HRID 872092 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:9]2[N:14]3[N:15]=[C:16]([CH3:19])[C:17](I)=[C:13]3[N:12]=[C:11]([N:20]3[CH2:24][CH2:23][CH2:22][C@H:21]3[CH2:25][OH:26])[CH:10]=2)[CH:5]=[CH:6][C:7]=1[F:8].[CH3:27][O:28][C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1.C1(C)C=CC=CC=1.C([O-])(O)=O.[Na+]>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.C(O)C>[F:1][C:2]1[CH:3]=[C:4]([C:9]2[N:14]3[N:15]=[C:16]([CH3:19])[C:17]([C:32]4[CH:33]=[CH:34][C:29]([O:28][CH3:27])=[CH:30][CH:31]=4)=[C:13]3[N:12]=[C:11]([N:20]3[CH2:24][CH2:23][CH2:22][C@H:21]3[CH2:25][OH:26])[CH:10]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

7

Reactant 4

HCID 1140TolueneHCID 201262(4-Methoxyphenyl)boronic acidHCID 516892Sodium BicarbonateHCID 68026319(S)-(1-(7-(3,4-difluorophenyl)-3-iodo-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)pyrrolidin-2-yl)methanol

Product 1

HCID 66635745(S)-{1-[7-(3,4-difluorophenyl)-3-(4-methoxyphenyl)-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)pyrrolidin-2-yl)methanolYield 97.7%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
85 °C

Procedure

(S)-(1-(7-(3,4-Difluorophenyl)-3-iodo-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)pyrrolidin-2-yl)methanol (62 mg), 4-methoxyphenylboronic acid (27 mg) and tetrakis(triphenylphosphine)palladium (10 mg) are added to toluene (8 mL), ethanol (3 mL) and 1 N NaHCO3 aqueous solution (1.5 mL) and stirred for 6 hours under argon atmosphere at 85° C. After cooling to room temperature, the reaction solvent is removed by distillation under reduced pressure. The remainder is extracted with ethyl acetate and water. The organic layer is washed with brine and dehydrated with anhydrous MgSO4. The dehydrated organic layer is distilled under reduced pressure, concentrated and purified by column chromatography to yield the target compound (58 mg).

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe reaction solvent is removed by distillation under reduced pressure
  3. extractionThe remainder is extracted with ethyl acetate and water
  4. washThe organic layer is washed with brine
  5. distillationThe dehydrated organic layer is distilled under reduced pressure
  6. concentrationconcentrated
  7. custompurified by column chromatography

Sources & evidence

ORD record
ord-9e321cc5d0fa4dcabdd91ecf5dbd5d7b
Source dataset
uspto-grants-2015_03
Patent number
US08975264B2

Reaction notes

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