Acetic Acid → (S)-2-tert-butoxy-2-(7-(4-chlorophenyl)-2-(1,3-dimethyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-5-methylbenzo[d]thiazol-6-yl)acetic acid

HRID 879640Notes

Reaction equation

HRID 879640 reaction equation
[C:1]([O:5][C@@H:6]([C:11]1[C:30]([CH3:31])=[CH:29][C:14]2[N:15]=[C:16]([C:18]3[N:19]=[CH:20][C:21]4[N:26]([CH3:27])[N:25]=[C:24]([CH3:28])[C:22]=4[N:23]=3)[S:17][C:13]=2[C:12]=1[C:32]1[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][CH:33]=1)[C:7]([O:9]C)=[O:8])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].C(O)(=O)C.CN(C=O)C>C1COCC1.CO>[C:1]([O:5][C@@H:6]([C:11]1[C:30]([CH3:31])=[CH:29][C:14]2[N:15]=[C:16]([C:18]3[N:19]=[CH:20][C:21]4[N:26]([CH3:27])[N:25]=[C:24]([CH3:28])[C:22]=4[N:23]=3)[S:17][C:13]=2[C:12]=1[C:32]1[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][CH:33]=1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 6228DimethylformamideHCID 14798Sodium HydroxideHCID 86700447(S)-methyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-2-(1,3-dimethyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-5-methylbenzo[d]thiazol-6-yl)acetate

Product 1

HCID 86700449(S)-2-tert-butoxy-2-(7-(4-chlorophenyl)-2-(1,3-dimethyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-5-methylbenzo[d]thiazol-6-yl)acetic acid

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of (S)-methyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-2-(1,3-dimethyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-5-methylbenzo[d]thiazol-6-yl)acetate (38 mg, 0.07 mmol) and 5M sodium hydroxide (0.28 mL, 1.4 mmol) in THF (2 mL) and MeOH (0.5 mL) was stirred at 50° C. for 2 h. Reaction mixture was cooled to rt, acetic acid (88 μL) and DMF (0.3 mL) were added and reaction mixture was concentrated to ˜0.3 mL, filtered, purified by Gilson HPLC (Gemini, 5 to 100% ACN/H2O+0.1% TFA) and lyophilized to give desired product. LCMS-ESI+: calc'd for C27H27ClN5O3S: 536.1 (M+H+); Found: 536.2 (M+H+); 1H NMR (400 MHz, CD3OD) δ 9.29 (s, 1H), 7.92 (s, 1H), 7.71 (d, J=8.0 Hz, 1H), 7.62 (br s, 3H), 5.28 (s, 1H), 4.13 (s, 3H), 2.63 (s, 6H), 0.98 (s, 9H).

Workup

  1. customReaction mixture
  2. customreaction mixture
  3. concentrationwas concentrated to ˜0.3 mL
  4. filtrationfiltered
  5. custompurified by Gilson HPLC (Gemini, 5 to 100% ACN/H2O+0.1% TFA)

Sources & evidence

ORD record
ord-b702142991e044608a3e0fb50e92418e
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

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