catecholborane THF → (S)-methyl 2-(2-(3-chlorophenyl)-7-(4-fluorophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate

HRID 472861Notes

Reaction equation

HRID 472861 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:30]=[C:11]3[N:12]=[C:13]([CH3:29])[C:14]([C:23](=[O:28])[C:24]([O:26][CH3:27])=[O:25])=[C:15]([C:16]4[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=4)[N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.CB1N2CCC[C@@H]2C(C2C=CC=CC=2)(C2C=CC=CC=2)O1.C1(C)C=CC=CC=1.[B]1OC2C(=CC=CC=2)O1.C1COCC1>C1(C)C=CC=CC=1.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:30]=[C:11]3[N:12]=[C:13]([CH3:29])[C:14]([C@H:23]([OH:28])[C:24]([O:26][CH3:27])=[O:25])=[C:15]([C:16]4[CH:17]=[CH:18][C:19]([F:22])=[CH:20][CH:21]=4)[N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 15900295catecholborane THFHCID 66693072Methyl 2-(2-(3-chlorophenyl)-7-(4-fluorophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetateHCID 86670277(R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole toluene

Product 1

HCID 66692935(S)-methyl 2-(2-(3-chlorophenyl)-7-(4-fluorophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetateYield 94%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-35 °C

Procedure

To a stirred solution of methyl 2-(2-(3-chlorophenyl)-7-(4-fluorophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetate (0.083 g, 0.196 mmol) in toluene (5 mL) was added 1M (R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole/toluene (0.039 ml, 0.039 mmol) and cooled to −35° C. To this was added dropwise 1M catecholborane/THF (0.294 ml, 0.294 mmol) over 10 min and stirred for additional 20 min. Then, the reaction was slowly warmed to −15 C over 30 min, diluted with EtOAc (10 ml) and quenched with sat. Na2CO3 (5 mL). The resulting mixture was vigorously stirred for 30 min, aq. larer removed and organic layer washed with sat. Na2CO3 (2×5 mL), dried (Na2SO4), filtered, concentrated to yellow residue which was purified by prep-HPLC to afford (S)-methyl 2-(2-(3-chlorophenyl)-7-(4-fluorophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate (0.08 g, 0.184 mmol, 94% yield) as solid. 1H NMR (500 MHz, CDCl3) δ: 7.82 (s, 1H), 7.75-7.68 (m, 1H), 7.68-7.58 (m, 2H), 7.34-7.24 (m, 4H), 6.88 (s, 1H), 5.16 (s, 1H), 3.78 (s, 3H), 3.69-3.34 (br.s., 1H), 2.58 (s, 3H). LCMS (M+H) calcd for C22H18ClFN3O3: 426.1. found: 426.2.

Workup

  1. temperatureThen, the reaction was slowly warmed to −15 C over 30 min
  2. customquenched with sat. Na2CO3 (5 mL)
  3. stirringThe resulting mixture was vigorously stirred for 30 min
  4. customaq. larer removed
  5. washorganic layer washed with sat. Na2CO3 (2×5 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated to yellow residue which
  9. customwas purified by prep-HPLC

Sources & evidence

ORD record
ord-e03cfafa2aac43ccabaca70be5cf8d10
Source dataset
uspto-grants-2014_01
Patent number
US08633200B2

Reaction notes

Loading…