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

HRID 879642Notes

Reaction equation

HRID 879642 reaction equation
[C:1]([O:5][C@@H:6]([C:11]1[C:36]([CH3:37])=[CH:35][C:14]2[N:15]=[C:16]([C:18]3[CH:23]=[CH:22][N:21]=[C:20]([C:24]4[N:25]=[CH:26][C:27]5[N:32]([CH3:33])[N:31]=[C:30]([CH3:34])[C:28]=5[N:29]=4)[CH:19]=3)[S:17][C:13]=2[C:12]=1[C:38]1[CH:43]=[CH:42][C:41]([Cl:44])=[CH:40][CH:39]=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:36]([CH3:37])=[CH:35][C:14]2[N:15]=[C:16]([C:18]3[CH:23]=[CH:22][N:21]=[C:20]([C:24]4[N:25]=[CH:26][C:27]5[N:32]([CH3:33])[N:31]=[C:30]([CH3:34])[C:28]=5[N:29]=4)[CH:19]=3)[S:17][C:13]=2[C:12]=1[C:38]1[CH:39]=[CH:40][C:41]([Cl:44])=[CH:42][CH:43]=1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 6228DimethylformamideHCID 14798Sodium HydroxideHCID 86700450(S)-methyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-2-(2-(1,3-dimethyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl)pyridin-4-yl)-5-methylbenzo[d]thiazol-6-yl)acetate

Product 1

HCID 86700451(S)-2-tert-butoxy-2-(7-(4-chlorophenyl)-2-(2-(1,3-dimethyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl)pyridin-4-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-(2-(1,3-dimethyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl)pyridin-4-yl)-5-methylbenzo[d]thiazol-6-yl)acetate (7.7 mg, 0.012 mmol) and 5M sodium hydroxide (20 μL, 0.012 mmol) in THF (1 mL) and MeOH (0.2 mL) was stirred at 50° C. for 2 h. Reaction mixture was cooled to rt, acetic acid (15 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 C32H30ClN6O3S: 613.2 (M+H+); Found: 613.2 (M+H+); 1H NMR (400 MHz, CD3OD) δ 9.41 (s, 1H), 9.28 (s, 1H), 8.85 (s, 1H), 8.25 (s, 1H), 7.99 (s, 1H), 7.76-7.43 (m, 4H), 5.28 (s, 1H), 4.16 (s, 3H), 2.71 (s, 3H), 2.65 (s, 3H), 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-4a03fc0d7cd24c7f99e2ef864299e9c1
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

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