Sodium Hydroxide → HCID 66551737, compound

HRID 1410016Notes

Reaction equation

HRID 1410016 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:11][C:12]2[C:13]3[N:39]=[CH:38][S:37][C:14]=3[N:15]=[C:16]([N:18]3[CH2:22][CH2:21][CH:20]([NH:23][C:24]([C:26]4[CH:34]=[CH:33][C:29]([C:30]([O-:32])=[O:31])=[C:28]([O:35][CH3:36])[CH:27]=4)=[O:25])[CH2:19]3)[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:39]=[CH:38][S:37][C:14]=3[N:15]=[C:16]([N:18]3[CH2:22][CH2:21][CH:20]([NH:23][C:24]([C:26]4[CH:34]=[CH:33][C:29]([C:30]([OH:32])=[O:31])=[C:28]([O:35][CH3:36])[CH:27]=4)=[O:25])[CH2:19]3)[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 86671782HCID 86671782, compound

Product 1

HCID 66551737HCID 66551737, compoundYield 39%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 4-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-ylcarbamoyl)-2-methoxybenzoate (80 mg, 0.14 mmol) in 5 mL of THF and 5 mL of methanol was added a solution of 1N NaOH (5 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 suspension was filtered and dried. The crude 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 55% acetonitrile/45% water (0.1% TFA V/V) in a linear fashion after just 9 min) to give 4-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-ylcarbamoyl)-2-methoxybenzoic acid (30 mg, 39%) as white solid. 1H NMR (300 MHz, DMSO): δ 9.66 (s, 1H), 8.83 (s, 1H), 8.74-8.72 (m, 1H), 7.88 (brs, 1H), 7.66 (d, 1H, J=7.8 Hz), 7.50-7.46 (m, 3H), 6.91 (d, 1H, J=8.7 Hz), 4.59 (brs, 1H), 3.87 (s, 4H), 3.76-3.72 (m, 8H), 2.27 (brs, 1H), 2.09 (brs, 1H). LC-MS: 550.8 [M+H]+, tR=1.38 min. HPLC: 98.09% at 214 nm, 96.40% at 254 nm, tR=4.64 min.

Workup

  1. additionAfter the addition
  2. customThe solvent was evaporated
  3. additionthe residue was diluted with water
  4. filtrationThe suspension was filtered
  5. customdried
  6. customThe crude was purified by preparative HPLC (Gemini 5u C18 150×21.2 mm
  7. wait20% acetonitrile/80% water (0.1% TFA V/V) initially, and then proceed to 55% acetonitrile/45% water (0.1% TFA V/V) in a linear fashion after just 9 min

Sources & evidence

ORD record
ord-8c59c1e72eef4b8b81e34e4d84cdbb6c
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

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