tert-Butyl acetate → (S)-methyl 2-(tert-butoxy)-2-(2-(3-chlorophenyl)-7-isopropyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate

HRID 472854Notes

Reaction equation

HRID 472854 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@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.C(O[C:31]([CH3:34])([CH3:33])[CH3:32])(=O)C.Cl(O)(=O)(=O)=O>C(Cl)Cl.CCOCC>[C:31]([O:24][C@@H:19]([C:14]1[C:13]([CH3:25])=[N:12][C:11]2[N:10]([N:9]=[C:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=3)[CH:26]=2)[C:15]=1[CH:16]([CH3:18])[CH3:17])[C:20]([O:22][CH3:23])=[O:21])([CH3:34])([CH3:33])[CH3:32]

Participants

6

Reactant 3

HCID 10908tert-Butyl acetateHCID 24247Perchloric AcidHCID 66693747(S)-methyl 2-(2-(3-chlorophenyl)-7-isopropyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate

Product 1

HCID 66691616(S)-methyl 2-(tert-butoxy)-2-(2-(3-chlorophenyl)-7-isopropyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetateYield 131.9%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (S)-methyl 2-(2-(3-chlorophenyl)-7-isopropyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate (0.069 g, 0.185 mmol) and tert-butyl acetate (1.247 ml, 9.23 mmol) in CH2Cl2 (5 mL) was added 70% perchloric acid (0.048 ml, 0.554 mmol) at rt. After 3 h, the reaction mixture was diluted with Et2O (35 mL), washed with sat Na2CO3 (2×5 mL), brine (5 mL), dried (Na2SO4), filtered and concentrated to give colorless paste which was purified by prep-HPLC to afford (S)-methyl 2-(tert-butoxy)-2-(2-(3-chlorophenyl)-7-isopropyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate (0.0496 g, 0.244 mmol, 62.5% yield) as white solid. 1H NMR (500 MHz, CDCl3) δ: 7.98 (t, J=1.7 Hz, 1H), 7.87 (dt, J=7.6, 1.4 Hz, 1H), 7.41-7.32 (m, 2H), 6.77 (s, 1H), 5.42 (s, 1H), 4.07 (dt, J=13.6, 6.9 Hz, 1H), 3.71 (s, 3H), 2.73 (s, 3H), 1.68 (d, J=7.0 Hz, 3H), 1.56 (d, J=7.0 Hz, 3H), 1.26 (s, 9H). LCMS (M+H) calcd for C23H29ClN3O3: 430.19. found: 430.3.

Workup

  1. washwashed
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give colorless paste which
  6. customwas purified by prep-HPLC

Sources & evidence

ORD record
ord-d07a0b08a8b84052800cdd8fca3da824
Source dataset
uspto-grants-2014_01
Patent number
US08633200B2

Reaction notes

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