Lithium hydroxide, monohydrate → HCID 71251279, compound

HRID 2171917Notes

Reaction equation

HRID 2171917 reaction equation
[C:1]([N:5]([NH:12][C:13]1[C:18]([F:19])=[CH:17][N:16]=[C:15]([C:20]2[C:28]3[C:23](=[N:24][CH:25]=[C:26]([C:29]([F:32])([F:31])[F:30])[CH:27]=3)[NH:22][CH:21]=2)[N:14]=1)[CH2:6][C:7]([O:9]CC)=[O:8])([CH3:4])([CH3:3])[CH3:2].O.[OH-].[Li+]>C1COCC1.O>[C:1]([N:5]([CH2:6][C:7]([OH:9])=[O:8])[NH:12][C:13]1[C:18]([F:19])=[CH:17][N:16]=[C:15]([C:20]2[C:28]3[C:23](=[N:24][CH:25]=[C:26]([C:29]([F:32])([F:30])[F:31])[CH:27]=3)[NH:22][CH:21]=2)[N:14]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 71247923HCID 71247923, compound2×

Product 1

HCID 71251279HCID 71251279, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl 2-[tert-butyl-[[5-fluoro-2-[5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyrimidin-4-yl]amino]amino]acetate, 155a, (0.200 g, 0.440 mmol) in THF (40 mL) was added a solution of lithium hydroxide hydrate (0.074 g, 1.760 mmol) in H2O (4 mL). The reaction mixture was stirred at room temperature overnight. The reaction mixture concentrated in vacuo to remove the THF. The remaining aqueous phase was diluted to 8 mL and the solution was used directly in a preparatory HPLC. The product precipitated when the fraction was concentrated on rotavaporator. The solid was filtered and dried in desiccator with P2O5 to afford 120 mg of the desired product: 1H NMR (400 MHz, d6-DMSO) δ 12.65 (s, 1H), 12.41 (s, 1H), 9.28 (s, 1H), 8.86 (s, 1H), 8.65 (s, 1H), 8.30 (d, J=3.5 Hz, 2H), 3.97-3.70 (m, 1H), 3.51 (s, 1H), 1.18 (s, 9H); LCMS Gradient 10-90%, 0.1% formic acid, 5 minutes, C18/ACN, Retention Time=2.92 min, (M+H) 427.40

Workup

  1. concentrationThe reaction mixture concentrated in vacuo
  2. customto remove the THF
  3. additionThe remaining aqueous phase was diluted to 8 mL
  4. customThe product precipitated when the fraction
  5. concentrationwas concentrated on rotavaporator
  6. filtrationThe solid was filtered
  7. dry with materialdried in desiccator with P2O5

Sources & evidence

ORD record
ord-05193ad11b04450096606ac890c6fcb7
Source dataset
uspto-grants-2015_06
Patent number
US09051319B2

Reaction notes

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