Tetrahydrofuran → (S)-methyl 2-(7-chloro-5-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate

HRID 574335Notes

Reaction equation

HRID 574335 reaction equation
[Cl:1][C:2]1[N:7]2[N:8]=[C:9]([C:11]3[CH:20]=[CH:19][C:18]4[CH2:17][CH2:16][CH2:15][CH2:14][C:13]=4[CH:12]=3)[CH:10]=[C:6]2[N:5]=[C:4]([CH3:21])[C:3]=1[C:22](=[O:27])[C:23]([O:25][CH3:26])=[O:24].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[N:7]2[N:8]=[C:9]([C:11]3[CH:20]=[CH:19][C:18]4[CH2:17][CH2:16][CH2:15][CH2:14][C:13]=4[CH:12]=3)[CH:10]=[C:6]2[N:5]=[C:4]([CH3:21])[C:3]=1[C@H:22]([OH:27])[C:23]([O:25][CH3:26])=[O:24]

Participants

7

Reactant 3

HCID 8028TetrahydrofuranHCID 86670277(R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole tolueneHCID 86670287Methyl 2-(7-chloro-5-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetate

Product 1

HCID 86670288(S)-methyl 2-(7-chloro-5-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetateYield 88.2%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
-35 °C

Procedure

To a stirred yellow solution of methyl 2-(7-chloro-5-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetate (1 g, 2.61 mmol) in anhydrous toluene (25 mL) was added 1.1M (R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole/toluene (0.947 mL, 1.042 mmol). The mixture was cooled to −35° C. and a solution of 1M catechoborane/THF (3.65 mL, 3.65 mmol) was added over 10 min. After 30 min, the reaction mixture was slowly warmed to −15 C and stirred for additional 30 min. and diluted with EtOAc (30 mL) and sat. Na2CO3 (10 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 silica gel chromatography (5-70% EtOAc/hexane) to afford desired (S)-methyl 2-(7-chloro-5-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate (888 mg, 2.301 mmol, 88% yield) as off-white solid. EE=95.4% 1H NMR (500 MHz, CDCl3) δ 7.77-7.71 (m, 2H), 7.19 (d, J=7.6 Hz, 1H), 6.93 (s, 1H), 5.78 (d, J=2.7 Hz, 1H), 3.86 (s, 3H), 3.56 (d, J=2.7 Hz, 1H), 2.89-1.81 (m, 4H), 2.64 (s, 3H), 1.86 (dt, J=6.5, 3.3 Hz, 4H). LCMS (M+H)=386.3.

Workup

  1. temperaturethe reaction mixture was slowly warmed to −15 C
  2. stirringThe mixture was stirred vigorously for 30 min
  3. washthe organic phase washed
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customthe residue was purified by silica gel chromatography (5-70% EtOAc/hexane)

Sources & evidence

ORD record
ord-e926c827eb194aad97ed44906325e037
Source dataset
uspto-grants-2015_05
Patent number
US09034882B2

Reaction notes

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