Sodium Hydroxide → (S)-4-(7-(3-methoxy-5-(2-methylpyrrolidin-1-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoic acid

HRID 1410112Notes

Reaction equation

HRID 1410112 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:15][C:16]2[C:17]3[N:34]=[CH:33][S:32][C:18]=3[N:19]=[C:20]([C:22]3[CH:31]=[CH:30][C:25]([C:26]([O:28]C)=[O:27])=[CH:24][CH:23]=3)[N:21]=2)[CH:6]=[C:7]([N:9]2[CH2:13][CH2:12][CH2:11][C@@H:10]2[CH3:14])[CH:8]=1.[OH-].[Na+]>O1CCOCC1.O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:15][C:16]2[C:17]3[N:34]=[CH:33][S:32][C:18]=3[N:19]=[C:20]([C:22]3[CH:23]=[CH:24][C:25]([C:26]([OH:28])=[O:27])=[CH:30][CH:31]=3)[N:21]=2)[CH:6]=[C:7]([N:9]2[CH2:13][CH2:12][CH2:11][C@@H:10]2[CH3:14])[CH:8]=1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 68379626(S)-methyl 4-(7-(3-methoxy-5-(2-methylpyrrolidin-1-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoate

Product 1

HCID 68379519(S)-4-(7-(3-methoxy-5-(2-methylpyrrolidin-1-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoic acidYield 43.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
30 °C

Procedure

The mixture of (S)-methyl 4-(7-(3-methoxy-5-(2-methylpyrrolidin-1-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoate (121 mg, 0.25 mmol) and NaOH (102 mg, 2.54 mmol) in dioxane (20 mL) and H2O (10 mL) was heated to 30° C. for 2 h. The reaction mixture was concentrated and the aqueous residue was adjusted to pH˜4 by the addition of conc. HCl. The solution was extracted with ethyl acetate (10 mL×3), then combined organics dried over Na2SO4 and concentrated to afford (S)-4-(7-(3-methoxy-5-(2-methylpyrrolidin-1-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoic acid (50 mg, crude) as yellow solid which was used to next step without purification. LC-MS: 462 [M+H]+, tR=1.699 min.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additionthe aqueous residue was adjusted to pH˜4 by the addition of conc. HCl
  3. extractionThe solution was extracted with ethyl acetate (10 mL×3)
  4. dry with materialcombined organics dried over Na2SO4
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-cd8c13d8dd21406e82f3886ee045f7ca
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

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