Sodium Hydroxide → 3-(7-(3-(2-Oxa-6-azaspiro[3.3]heptan-6-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoic acid

HRID 1410092Notes

Reaction equation

HRID 1410092 reaction equation
[CH2:1]1[C:4]2([CH2:7][N:6]([C:8]3[CH:9]=[C:10]([NH:14][C:15]4[C:16]5[N:33]=[CH:32][S:31][C:17]=5[N:18]=[C:19]([C:21]5[CH:22]=[C:23]([CH:28]=[CH:29][CH:30]=5)[C:24]([O:26]C)=[O:25])[N:20]=4)[CH:11]=[CH:12][CH:13]=3)[CH2:5]2)[CH2:3][O:2]1.[OH-].[Na+]>C1COCC1.CO>[CH2:3]1[C:4]2([CH2:7][N:6]([C:8]3[CH:9]=[C:10]([NH:14][C:15]4[C:16]5[N:33]=[CH:32][S:31][C:17]=5[N:18]=[C:19]([C:21]5[CH:22]=[C:23]([CH:28]=[CH:29][CH:30]=5)[C:24]([OH:26])=[O:25])[N:20]=4)[CH:11]=[CH:12][CH:13]=3)[CH2:5]2)[CH2:1][O:2]1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 68379407Methyl 3-(7-(3-(2-oxa-6-azaspiro[3.3]heptan-6-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoate

Product 1

HCID 665501163-(7-(3-(2-Oxa-6-azaspiro[3.3]heptan-6-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoic acidYield 15%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of methyl 3-(7-(3-(2-oxa-6-azaspiro[3.3]heptan-6-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoate (70 mg, 0.15 mmol) in 5 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 15 hours. The solvent was evaporated and the residue was diluted with water and adjusted to pH=2 by HCl (aq.). The precipitate was filtered, the cake 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: 40% acetonitrile/60% 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 3-(7-(3-(2-oxa-6-azaspiro[3.3]heptan-6-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoic acid (10 mg, 15%). 1H NMR (300 MHz, DMSO): δ 10.13 (s, 1H), 9.41 (s, 1H), 9.00 (s, 1H), 8.66 (d, 1H, J=8.1 Hz), 8.12-8.10 (m, 1H), 7.70 (t, 1H, J=7.9 Hz), 7.45 (s, 1H), 7.24-7.18 (m, 2H), 6.23 (d, 1H, J=7.5 Hz), 4.75 (s, 4H), 4.03 (s, 4H). LC-MS: 446 [M+H]+, tR=1.59 min. HPLC: 97.95% at 214 nm, 100% at 254 nm, tR=7.31 min.

Workup

  1. additionAfter the addition
  2. customThe solvent was evaporated
  3. additionthe residue was diluted with water
  4. filtrationThe precipitate was filtered
  5. customthe cake was purified by preparative HPLC (Gemini 5u C18 150×21.2 mm
  6. wait40% acetonitrile/60% 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-3fbcfb31660f4a83b5a88b47119171ab
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

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