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

HRID 472858Notes

Reaction equation

HRID 472858 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:27]=[C:11]3[N:12]=[C:13]([CH3:26])[C:14]([C@H:20]([OH:25])[C:21]([O:23][CH3:24])=[O:22])=[C:15]([CH2:16][CH:17]([CH3:19])[CH3:18])[N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.C(O[C:32]([CH3:35])([CH3:34])[CH3:33])(=O)C>C(Cl)Cl.CCOCC>[C:32]([O:25][C@@H:20]([C:14]1[C:13]([CH3:26])=[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:27]=2)[C:15]=1[CH2:16][CH:17]([CH3:19])[CH3:18])[C:21]([O:23][CH3:24])=[O:22])([CH3:35])([CH3:34])[CH3:33]

Participants

5

Reactant 2

HCID 10908tert-Butyl acetateHCID 66693831(S)-methyl 2-(2-(3-chlorophenyl)-7-isobutyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate

Product 1

HCID 66693018(S)-methyl 2-(tert-butoxy)-2-(2-(3-chlorophenyl)-7-isobutyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetateYield 52.9%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (S)-methyl 2-(2-(3-chlorophenyl)-7-isobutyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate (0.059 g, 0.152 mmol) and tert-butyl acetate (1 ml, 7.40 mmol) in CH2Cl2 (3 mL) was added 70% perchloric aci (0.039 ml, 0.456 mmol) at rt. After 2 h, the reaction was diluted with Et2O (50 mL), washed with sat. Na2CO3 (2×5 mL), dried (Na2SO4), filtered and concentrated to give yellow solid which was purified by prep-HPLC to afford (S)-methyl 2-(tert-butoxy)-2-(2-(3-chlorophenyl)-7-isobutyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate (0.0357 g, 0.080 mmol, 52.9% yield) as brown paste. 1H NMR (500 MHz, CDCl3) δ: 7.97 (t, J=1.7 Hz, 1H), 7.86 (dt, J=7.6, 1.3 Hz, 1H), 7.40-7.31 (m, 2H), 6.79 (s, 1H), 5.36 (s, 1H), 3.70 (s, 3H), 3.53 (dd, J=13.4, 7.6 Hz, 1H), 3.14 (dd, J=13.4, 7.0 Hz, 1H), 2.69 (s, 3H), 2.65-2.54 (m, 1H), 1.25 (s, 9H), 1.03 (d, J=6.7 Hz, 3H), 0.98 (d, J=6.7 Hz, 3H). LCMS (M+H) calcd for C24H31ClN3O3: 444.21. found: 444.3.

Workup

  1. washwashed with sat. Na2CO3 (2×5 mL)
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give yellow solid which
  6. customwas purified by prep-HPLC

Sources & evidence

ORD record
ord-cd3a8f35daf84d2e84b8574a6b43bde0
Source dataset
uspto-grants-2014_01
Patent number
US08633200B2

Reaction notes

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