Sodium Hydroxide → 4-(3-(7-(3,4-Dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzamido)-2-methoxybenzoic acid

HRID 1410024Notes

Reaction equation

HRID 1410024 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:11][C:12]2[C:13]3[N:41]=[CH:40][S:39][C:14]=3[N:15]=[C:16]([C:18]3[CH:19]=[C:20]([CH:36]=[CH:37][CH:38]=3)[C:21]([NH:23][C:24]3[CH:33]=[CH:32][C:27]([C:28]([O:30]C)=[O:29])=[C:26]([O:34][CH3:35])[CH:25]=3)=[O:22])[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[OH-].[Na+]>C1COCC1.CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:11][C:12]2[C:13]3[N:41]=[CH:40][S:39][C:14]=3[N:15]=[C:16]([C:18]3[CH:19]=[C:20]([CH:36]=[CH:37][CH:38]=3)[C:21]([NH:23][C:24]3[CH:33]=[CH:32][C:27]([C:28]([OH:30])=[O:29])=[C:26]([O:34][CH3:35])[CH:25]=3)=[O:22])[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 68379396Methyl 4-(3-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzamido)-2-methoxybenzoate

Product 1

HCID 665519344-(3-(7-(3,4-Dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzamido)-2-methoxybenzoic acidYield 31%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of methyl 4-(3-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzamido)-2-methoxybenzoate (100 mg, 0.175 mmol) in 20 mL of THF and 5 mL of methanol was added a solution of 1N NaOH (2 mL) at room temperature. After the addition, the reaction was stirred at this temperature for 16 hours. The solvent was evaporated and the residue was diluted with water and adjusted to pH=2 by HCl (aq.). The mixture was concentrated by rotary evaporation. The residue was purified by preparative HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 ml/inj, flow rate: 20 ml/min; wavelength: 214 nm and 254 nm; the gradient conditions are: 20% acetonitrile/80% water (0.1% TFA V/V) initially, and then proceed to 70% acetonitrile/30% water (0.1% TFA V/V) in a linear fashion after just 9 min.) to give 4-(3-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzamido)-2-methoxybenzoic acid (30 mg, 31%). 1H NMR (300 MHz, DMSO): δ 10.70 (s, 1H), 10.21 (s, 1H), 9.41 (s, 1H), 8.96 (s, 1H), 8.62 (d, 1H, J=7.5 Hz), 8.09 (d, 1H, J=7.8 Hz), 7.84 (s, 1H), 7.77-7.70 (m, 3H), 7.54 (d, 1H, J=8.4 Hz), 6.99 (d, 1H, J=9.0 Hz), 3.84 (s, 3H), 3.81 (s, 3H), 3.74 (s, 3H). LC-MS: 558 [M+H]+, tR=1.54 min. HPLC: 100% at 214 nm, 100% at 254 nm, tR=6.02 min.

Workup

  1. additionAfter the addition
  2. customThe solvent was evaporated
  3. additionthe residue was diluted with water
  4. concentrationThe mixture was concentrated by rotary evaporation
  5. customThe residue was purified by preparative HPLC (Gemini 5u C18 150×21.2 mm
  6. wait20% acetonitrile/80% water (0.1% TFA V/V) initially, and then proceed to 70% acetonitrile/30% water (0.1% TFA V/V) in a linear fashion after just 9 min.

Sources & evidence

ORD record
ord-56a22645bb3547ce813ca9bd6bd66020
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

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