Sodium Hydroxide → 4-(1-(7-(3,4-Dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidine-3-carboxamido)-2-methoxybenzoic acid

HRID 1410081Notes

Reaction equation

HRID 1410081 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]([N:18]3[CH2:23][CH2:22][CH2:21][CH:20]([C:24]([NH:26][C:27]4[CH:36]=[CH:35][C:30]([C:31]([O:33]C)=[O:32])=[C:29]([O:37][CH3:38])[CH:28]=4)=[O:25])[CH2:19]3)[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[OH-].[Na+]>O1CCOCC1.O>[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]([N:18]3[CH2:23][CH2:22][CH2:21][CH:20]([C:24]([NH:26][C:27]4[CH:36]=[CH:35][C:30]([C:31]([OH:33])=[O:32])=[C:29]([O:37][CH3:38])[CH:28]=4)=[O:25])[CH2:19]3)[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 66549702Methyl 4-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidine-3-carboxamido)-2-methoxybenzoate

Product 1

HCID 683791104-(1-(7-(3,4-Dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidine-3-carboxamido)-2-methoxybenzoic acidYield 54.8%

Reagents, catalysts & solvents 1

HCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
35 °C

Procedure

To a solution of methyl 4-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidine-3-carboxamido)-2-methoxybenzoate (126 mg, 0.22 mmol) in dioxane/H2O (8 mL/8 mL) was added NaOH (75 mg, 1.9 mmol), the reaction mixture was heated to 35° C. with stirring for 1 hour, the dioxane was removed in vacuo, and the aqueous layer was adjusted to pH=4-5 with conc. HCl, the precipitate was collected by filtration and washed with methanol (5 mL) to afford 4-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidine-3-carboxamido)-2-methoxybenzoic acid (68 mg, 54.8%) as a off-white solid. 1H NMR (300 MHz, DMSO): δ 10.23 (s, 1H), 9.63 (s, 1H), 8.83 (s, 1H), 7.63 (d, 1H, J=2.1 Hz), 7.58 (d, 1H, J=8.4 Hz), 7.46 (s, 1H), 7.33 (dd, 1H, J1=8.7 Hz, J2=2.4 Hz), 7.14 (dd, 1H, J1=8.4 Hz, J2=1.5 Hz), 6.80-6.78 (m, 1H), 4.79 (d, 1H, J=11.7 Hz), 4.65 (d, 1H, J=12.6 Hz), 3.68-3.61 (m, 9H), 3.10-2.89 (m, 2H), 2.58-2.54 (m, 1H), 2.03-1.99 (m, 1H), 1.78-1.71 (m, 2H), 1.48-1.44 (m, 1H). LC-MS: 585 [M+H]+, tR=1.48 min. HPLC: 96.06% at 214 nm, 97.26% at 254 nm, tR=5.66 min.

Workup

  1. customthe dioxane was removed in vacuo
  2. filtrationthe precipitate was collected by filtration
  3. washwashed with methanol (5 mL)

Sources & evidence

ORD record
ord-070d703e36af4765a70cf07befff3237
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

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