Hydrochloric Acid → (S)-2-(tert-butoxy)-2-(2-(3-chlorophenyl)-7-cyclohexyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetic acid

HRID 472869Notes

Reaction equation

HRID 472869 reaction equation
[C:1]([O:5][C@@H:6]([C:11]1[C:12]([CH3:33])=[N:13][C:14]2[N:15]([N:23]=[C:24]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([Cl:32])[CH:27]=3)[CH:25]=2)[C:16]=1[CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1)[C:7]([O:9]C)=[O:8])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].Cl>CO>[C:1]([O:5][C@@H:6]([C:11]1[C:12]([CH3:33])=[N:13][C:14]2[N:15]([N:23]=[C:24]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([Cl:32])[CH:27]=3)[CH:25]=2)[C:16]=1[CH:17]1[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 66693715(S)-methyl 2-(tert-butoxy)-2-(2-(3-chlorophenyl)-7-cyclohexyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate

Product 1

HCID 66693600(S)-2-(tert-butoxy)-2-(2-(3-chlorophenyl)-7-cyclohexyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetic acidYield 90.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of (S)-methyl 2-(tert-butoxy)-2-(2-(3-chlorophenyl)-7-cyclohexyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate (0.048 g, 0.102 mmol) and 1M NaOH (1.021 ml, 1.021 mmol) in MeOH (5 mL) was heated at reflux for h. Then, cooled, neutralized with 1M HCl (0.8 mL), concentrated and the residue was taken up in Et2O (25 mL), washed with water (5 mL), brine (5 mL), dried (MgSO4), filtered and concentrated to give (S)-2-(tert-butoxy)-2-(2-(3-chlorophenyl)-7-cyclohexyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetic acid (0.0426 g, 0.092 mmol, 90% yield) as light yellow solid. 1H NMR (500 MHz, CDCl3) δ: 7.95 (s, 1H), 7.86 (d, J=7.3 Hz, 1H), 7.42-7.32 (m, 2H), 6.77 (s, 1H), 5.46 (br. s., 1H), 3.43 (br. s., 1H), 2.97-2.84 (m, 2H), 2.72 (br. s., 3H), 1.98-1.70 (m, 4H), 1.58-1.32 (m, 4H), 1.28 (br. s., 9H). LCMS (M+H) calcd for C25H31ClN3O3: 456.21. found: 456.3. Examples 150-157 were prepared using the synthetic route similar to Scheme 10.

Workup

  1. temperatureat reflux for h
  2. temperatureThen, cooled
  3. concentrationconcentrated
  4. washwashed with water (5 mL), brine (5 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-9b4d49c2cff844d2a9abaf4cb96c503c
Source dataset
uspto-grants-2014_01
Patent number
US08633200B2

Reaction notes

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