Tetrahydrofuran → (S)-methyl 2-(2-(3-chlorophenyl)-7-isopropyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate

HRID 472853Notes

Reaction equation

HRID 472853 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:26]=[C:11]3[N:12]=[C:13]([CH3:25])[C:14]([C:19](=[O:24])[C:20]([O:22][CH3:23])=[O:21])=[C:15]([CH:16]([CH3:18])[CH3:17])[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.C1COCC1>C1(C)C=CC=CC=1.CCOC(C)=O.C([O-])([O-])=O.[Na+].[Na+]>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:26]=[C:11]3[N:12]=[C:13]([CH3:25])[C:14]([C@H:19]([OH:24])[C:20]([O:22][CH3:23])=[O:21])=[C:15]([CH:16]([CH3:18])[CH3:17])[N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 3

HCID 8028TetrahydrofuranHCID 66692217Methyl 2-(2-(3-chlorophenyl)-7-isopropyl-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 66693747(S)-methyl 2-(2-(3-chlorophenyl)-7-isopropyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetateYield 66.9%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
-35 °C

Procedure

To a stirred yellow solution of methyl 2-(2-(3-chlorophenyl)-7-isopropyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetate (0.103 g, 0.277 mmol) in anhydrous toluene (5 mL) was added 1.1M (R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole/toluene (0.101 ml, 0.111 mmol). The mixture was cooled to −35° C. and a solution of 1M catechoborane/THF (0.388 ml, 0.388 mmol) was added over 10 min. After 30 min, the reaction mixture was slowly warmed to −15 C and diluted with EtOAc (5 mL) and sat. Na2CO3 (2 mL). The mixture was stirred vigorously for 30 min, and the organic phase washed with sat Na2CO3 (2×5 mL), dried (Na2SO4), filtered, concentrated and the residue was purified by prep-HPLC to give (S)-methyl 2-(2-(3-chlorophenyl)-7-isopropyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate (0.0693 g, 0.185 mmol, 66.9% yield) as white solid. 1H NMR (500 MHz, CDCl3) δ: 7.99 (t, J=1.5 Hz, 1H), 7.86 (dt, J=7.4, 1.5 Hz, 1H), 7.41-7.33 (m, 2H), 6.80 (s, 1H), 5.63 (s, 1H), 3.81 (s, 3H), 3.40 (br. s., 1H), 2.62 (s, 3H), 1.68 (d, J=7.0 Hz, 3H), 1.59 (d, J=7.0 Hz, 3H). LCMS (M+H) calcd for C19H21ClN3O3: 374.13. found: 374.2.

Workup

  1. temperaturethe reaction mixture was slowly warmed to −15 C
  2. washthe organic phase washed
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customthe residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-4b3852ca9c814c6aa1f213b4f135a0ad
Source dataset
uspto-grants-2014_01
Patent number
US08633200B2

Reaction notes

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