Potassium Carbonate → HCID 68053272, compound

HRID 472884Notes

Reaction equation

HRID 472884 reaction equation
[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:30])=[N:14][C:15]2[N:16]([N:19]=[C:20]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[CH:24]=3)[C:21]=2[CH3:22])[C:17]=1Cl)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2].[F:31][C:32]1[CH:33]=[C:34](B2OC(C)(C)C(C)(C)O2)[C:35]([CH3:42])=[C:36]2[C:41]=1[O:40][CH2:39][CH2:38][CH2:37]2.C([O-])([O-])=O.[K+].[K+]>CN(C=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>[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:30])=[N:14][C:15]2[N:16]([N:19]=[C:20]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[CH:24]=3)[C:21]=2[CH3:22])[C:17]=1[C:34]1[C:35]([CH3:42])=[C:36]2[C:41](=[C:32]([F:31])[CH:33]=1)[O:40][CH2:39][CH2:38][CH2:37]2)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 59606766HCID 59606766, compoundHCID 86670294(S)-ethyl 2-(tert-butoxy)-2-(7-chloro-2-(3-chlorophenyl)-3,5-dimethylpyrazolo[1,5-a]pyrimidin-6-yl)acetate

Product 1

HCID 68053272HCID 68053272, compoundYield 35.7%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

A solution of (S)-ethyl 2-(tert-butoxy)-2-(7-chloro-2-(3-chlorophenyl)-3,5-dimethylpyrazolo[1,5-a]pyrimidin-6-yl)acetate (0.207 g, 0.460 mmol), 2-(8-fluoro-5-methylchroman-6-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.151 g, 0.517 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.081 g, 0.070 mmol) in anhydrous DMF (4 mL) was treated with 2.0 M K2CO3 (0.55 mL, 1.100 mmol), degassed by nitrogen stream, then sealed and heated (110° C., microwave) for 60 min. The reaction slurry was filtered though a 0.45 micron syringe tip filter, and the filtrate was purified by biotage silica gel column, eluting with 0%-20% ethyl acetate in hexanes. Individual atropisomers eluted separately, and the early eluting isomer was concentrated under reduced pressure, affording the single isomer, (2S)-ethyl 2-(tert-butoxy)-2-(2-(3-chlorophenyl)-7-(8-fluoro-5-methylchroman-6-yl)-3,5-dimethylpyrazolo[1,5-a]pyrimidin-6-yl)acetate (0.095 g, 0.164 mmol, 35.7% yield) as a white glassy solid.

Workup

  1. customdegassed by nitrogen stream
  2. customsealed
  3. filtrationThe reaction slurry was filtered though a 0.45 micron syringe tip
  4. filtrationfilter
  5. customthe filtrate was purified by biotage silica gel column
  6. washeluting with 0%-20% ethyl acetate in hexanes
  7. washIndividual atropisomers eluted separately
  8. washthe early eluting isomer
  9. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-3166dfad3c44437f84090765fccdce86
Source dataset
uspto-grants-2014_01
Patent number
US08633200B2

Reaction notes

Loading…