Lithium hydroxide, monohydrate → HCID 178427251, compound

HRID 1055115Notes

Reaction equation

HRID 1055115 reaction equation
[F:1][C:2]1[C:3]([NH:18][CH:19]([C:26]2([CH3:31])[CH2:30][CH2:29][CH2:28][CH2:27]2)[CH2:20][C:21]([O:23]CC)=[O:22])=[N:4][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[C:14]([F:17])[CH:15]=3)[NH:10][N:9]=2)=[N:6][CH:7]=1.O.[OH-].[Li+]>C1COCC1.O>[F:1][C:2]1[C:3]([NH:18][CH:19]([C:26]2([CH3:31])[CH2:30][CH2:29][CH2:28][CH2:27]2)[CH2:20][C:21]([OH:23])=[O:22])=[N:4][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[C:14]([F:17])[CH:15]=3)[NH:10][N:9]=2)=[N:6][CH:7]=1

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 178471969HCID 178471969, compound2×

Product 1

HCID 178427251HCID 178427251, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of racemic ethyl 3-[[5-fluoro-2-(5-fluoro-1H-pyrazolo[3,4-b]pyridin-3-yl)pyrimidin-4-yl]amino]-3-(1-methylcyclopentyl)propanoate, 149a, (0.110 g, 0.256 mmol) in THF (30 mL) was added a solution of lithium hydroxide hydrate (0.043 g, 1.022 mmol) in H2O (20 mL). The reaction mixture was stirred at 70° C. overnight. The organic solvent was removed under reduced pressure and the remaining aqueous phase was used directly in the purification via preparatory HPLC. The resulting HPLC fractions were extracted with EtOAc. The organic phase was dried over MgSO4, filtered and the solvent was removed under reduced pressure to afford the desired product: 1H NMR (400 MHz, MeOD) δ 8.64 (dd, J=8.4, 2.4 Hz, 1H), 8.57 (s, 1H), 8.24 (d, J=4.4 Hz, 1H), 5.19 (d, J=8.7 Hz, 1H), 2.78 (qd, J=15.9, 6.6 Hz, 2H), 1.85-1.57 (m, 6H), 1.48 (dd, J=11.8, 6.0 Hz, 1H), 1.36 (dt, J=12.0, 6.0 Hz, 1H), 1.11 (s, 3H). LCMS Gradient 10-90%, 0.1% formic acid, 5 minutes, C18/ACN, Retention Time=2.37 min, (M+H) 403.22.

Workup

  1. customThe organic solvent was removed under reduced pressure
  2. customthe remaining aqueous phase was used directly in the purification via preparatory HPLC
  3. extractionThe resulting HPLC fractions were extracted with EtOAc
  4. dry with materialThe organic phase was dried over MgSO4
  5. filtrationfiltered
  6. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-19f1a86042f44b38862c3c76c403b7e8
Source dataset
uspto-grants-2016_07
Patent number
US09394302B2

Reaction notes

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