Sodium Hydroxide → 3-(7-(3-((1R,5S)-8-oxa-3-azabicyclo[3.2.1]octan-3-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoic acid

HRID 1410069Notes

Reaction equation

HRID 1410069 reaction equation
[C@@H:1]12[O:8][C@@H:5]([CH2:6][CH2:7]1)[CH2:4][N:3]([C:9]1[CH:10]=[C:11]([NH:15][C:16]3[C:17]4[N:34]=[CH:33][S:32][C:18]=4[N:19]=[C:20]([C:22]4[CH:23]=[C:24]([CH:29]=[CH:30][CH:31]=4)[C:25]([O:27]C)=[O:26])[N:21]=3)[CH:12]=[CH:13][CH:14]=1)[CH2:2]2.[OH-].[Na+]>O1CCOCC1.O>[C@@H:5]12[O:8][C@@H:1]([CH2:7][CH2:6]1)[CH2:2][N:3]([C:9]1[CH:10]=[C:11]([NH:15][C:16]3[C:17]4[N:34]=[CH:33][S:32][C:18]=4[N:19]=[C:20]([C:22]4[CH:23]=[C:24]([CH:29]=[CH:30][CH:31]=4)[C:25]([OH:27])=[O:26])[N:21]=3)[CH:12]=[CH:13][CH:14]=1)[CH2:4]2

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 68379578methyl 3-(7-(3-((1R,5S)-8-oxa-3-azabicyclo[3.2.1]octan-3-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoate

Product 1

HCID 665493303-(7-(3-((1R,5S)-8-oxa-3-azabicyclo[3.2.1]octan-3-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoic acidYield 46%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
30 °C

Procedure

The mixture of methyl 3-(7-(3-((1R,5S)-8-oxa-3-azabicyclo[3.2.1]octan-3-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoate (0.094 g, 0.2 mmol) and NaOH (0.079 g, 2.0 mmol) in dioxane (10 mL) and H2O (5 mL) was stirred at 30° C. for 2 h. It was concentrated, residue diluted with water, washed with ether (2×5 mL) and the aqueous layer was adjusted to pH=4 by the addition of conc. HCl, then the solid formed was filtered and purified by recrystallization (15 mL, MeOH:EtOAc:ether=5:20:100, v/v/v) to afford 3-(7-(3-((1R,5S)-8-oxa-3-azabicyclo[3.2.1]octan-3-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoic acid (0.042 g, 46%) as a yellow solid. 1H NMR (300 MHz, DMSO): δ 13.23 (s, 1H), 10.15 (s, 1H), 9.42 (s, 1H), 8.98 (s, 1H), 8.61 (d, 1H, J=7.8 Hz), 8.09 (d, 1H, J=7.8 Hz), 7.68-7.62 (m, 2H), 7.41 (d, 1H, J=8.1 Hz), 7.23 (t, 1H, J=8.4 Hz), 6.65 (d, 1H, J=8.4 Hz), 4.44 (s, 2H), 3.43-3.36 (m, 2H), 2.89 (d, 1H, J=9.3 Hz), 1.86 (s, 4H). LC-MS: 460 [M+H]+, tR=1.64 min. HPLC: 95.36% at 214 nm, 96.48% at 254 nm, tR=5.20 min.

Workup

  1. concentrationIt was concentrated
  2. additionresidue diluted with water
  3. washwashed with ether (2×5 mL)
  4. additionthe aqueous layer was adjusted to pH=4 by the addition of conc. HCl
  5. customthe solid formed
  6. filtrationwas filtered
  7. custompurified by recrystallization (15 mL, MeOH:EtOAc:ether=5:20:100, v/v/v)

Sources & evidence

ORD record
ord-59e5e67ccb4340c7a606dd6334ac6b77
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

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