Lithium Hydroxide → HCID 71511508, compound

HRID 1055145Notes

Reaction equation

HRID 1055145 reaction equation
[Li+].[OH-].[F:3][C:4]1[C:5]([NH:20][CH:21]([C:28]2([CH3:34])[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]2)[CH2:22][C:23]([O:25]CC)=[O:24])=[N:6][C:7]([C:10]2[C:18]3[C:13](=[N:14][CH:15]=[C:16]([F:19])[CH:17]=3)[NH:12][CH:11]=2)=[N:8][CH:9]=1>O.C1COCC1>[F:3][C:4]1[C:5]([NH:20][CH:21]([C:28]2([CH3:34])[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]2)[CH2:22][C:23]([OH:25])=[O:24])=[N:6][C:7]([C:10]2[C:18]3[C:13](=[N:14][CH:15]=[C:16]([F:19])[CH:17]=3)[NH:12][CH:11]=2)=[N:8][CH:9]=1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 71511507HCID 71511507, compound

Product 1

HCID 71511508HCID 71511508, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
95 °C

Procedure

LiOH (0.118 mg, 4.927 mmol) was added to a solution of ethyl 3-(5-fluoro-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-ylamino)-3-(1-methylcyclohexyl)-propanoate, 77, (0.23 g, 0.49 mmol) in water (5 mL) and THF (5 mL). The solution was stirred at 95° C. for 18 hours and then cooled to room temperature. The solvent was removed under reduced pressure. The residue was diluted with water (10 mL) and neutralized with 2N HCl. The resulting precipitate was extracted with EtOAc (3×10 mL). The organic phase was dried (MgSO4), filtered and concentrated in vacuo to afford 210 mg of the desired product as an off-white solid: 1H NMR (400 MHz, CD3OD) δ 8.78 (dd, J=9.7, 2.7 Hz, 1H), 8.16 (s, 2H), 7.99 (d, J=4.1 Hz, 1H), 5.20 (d, J=9.9 Hz, 1H), 2.86-2.69 (m, 1H), 2.53 (dd, J=14.7, 11.0 Hz, 1H), 1.76-1.56 (m, 2H), 1.53 (m, 4H), 1.29 (m, 4H), 1.02 (s, 3H); LCMS Gradient 10-90%, 0.1% formic acid, 5 minutes, C18/ACN, Retention Time=2.20 minutes (M+H) 416.27.

Workup

  1. temperaturecooled to room temperature
  2. customThe solvent was removed under reduced pressure
  3. additionThe residue was diluted with water (10 mL)
  4. extractionThe resulting precipitate was extracted with EtOAc (3×10 mL)
  5. dry with materialThe organic phase was dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f959c8fcb7f041cabdbca7d33ed8fac4
Source dataset
uspto-grants-2016_07
Patent number
US09394302B2

Reaction notes

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