Lithium Hydroxide → (R)-3-(5-cyano-3-fluoro-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-ylamino)-3-(1-methylcyclopentyl)propanoic acid

HRID 2171906Notes

Reaction equation

HRID 2171906 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([F:32])[C:6]([NH:19][CH:20]([C:26]2([CH3:31])[CH2:30][CH2:29][CH2:28][CH2:27]2)[CH2:21][C:22]([O:24]C)=[O:23])=[N:7][C:8]=1[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([F:18])[CH:16]=2)[NH:11][CH:10]=1)#[N:2].C(C1C=C(F)C(N[C@@H](C2(C)CCCC2)CC(OC)=O)=NC=1C1C2C(=NC=C(F)C=2)NC=1)#N.[OH-].[Li+]>C1COCC1.O>[C:1]([C:3]1[CH:4]=[C:5]([F:32])[C:6]([NH:19][C@@H:20]([C:26]2([CH3:31])[CH2:27][CH2:28][CH2:29][CH2:30]2)[CH2:21][C:22]([OH:24])=[O:23])=[N:7][C:8]=1[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([F:18])[CH:16]=2)[NH:11][CH:10]=1)#[N:2]

Participants

6

Reactant 3

HCID 3939Lithium HydroxideHCID 71247736HCID 71247736, compoundHCID 71247738(R)-methyl 3-(5-cyano-3-fluoro-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-ylamino)-3-(1-methylcyclopentyl)propanoate

Product 1

HCID 71251347(R)-3-(5-cyano-3-fluoro-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-ylamino)-3-(1-methylcyclopentyl)propanoic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of racemic methyl 3-(5-cyano-3-fluoro-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-ylamino)-3-(1-methylcyclopentyl)propanoate, 145a, (0.090 g, 0.204 mmol) in THF (30 mL) was added a solution of lithium hydroxide (0.035 g, 0.819 mmol) in H2O (10 mL). The reaction mixture was stirred at 70° C. overnight. The organic phase was removed under reduced pressure and the resulting residue was purified by preparatory HPLC. The appropriate HPLC fractions were extracted with EtOAc, and the solvent was removed under reduced pressure: 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=3.21 minutes (M+H) 426.25.

Workup

  1. customThe organic phase was removed under reduced pressure
  2. customthe resulting residue was purified by preparatory HPLC
  3. extractionThe appropriate HPLC fractions were extracted with EtOAc
  4. customthe solvent was removed under reduced pressure
  5. customLCMS Gradient 10-90%, 0.1% formic acid, 5 minutes

Sources & evidence

ORD record
ord-132903c808864567b77a64369ca14f9d
Source dataset
uspto-grants-2015_06
Patent number
US09051319B2

Reaction notes

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