Water → HCID 86718274, compound

HRID 407754Notes

Reaction equation

HRID 407754 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[N:24]=[CH:23][CH:22]=[C:21]([C:25]3[CH:30]=[C:29]([NH:31][C:32]4[CH:36]=[CH:35][N:34]([CH3:37])[N:33]=4)[C:28](=[O:38])[N:27]([CH3:39])[CH:26]=3)[C:18]=1[CH:19]=[O:20])[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].O.[OH-].[Li+]>C1COCC1.CC(O)C>[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[C:18]([CH2:19][OH:20])=[C:21]([C:25]3[CH:30]=[C:29]([NH:31][C:32]4[CH:36]=[CH:35][N:34]([CH3:37])[N:33]=4)[C:28](=[O:38])[N:27]([CH3:39])[CH:26]=3)[CH:22]=[CH:23][N:24]=1)[N:9]=[CH:8]2)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 962WaterHCID 3939Lithium HydroxideHCID 86718272HCID 86718272, compound

Product 1

HCID 86718274HCID 86718274, compoundYield 20%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 140c (270 mg, 0.50 mmol) in THF (5 mL), propan-2-ol (5 mL), and water (2 mL) was added lithium hydroxide (36 mg, 1.5 mmol). The reaction mixture was stirred at room temperature for 1 h and concentrated under reduced pressure. The residue was diluted with dichloromethane (20 mL) and water (10 mL). The organic layer was separated and the aqueous layer was extracted with dichloromethane (3×15 mL). The combined organic layer was washed with brine and concentrated under reduced pressure. The residue was purified by reverse-phase prep-HPLC to afford 140 (53 mg, 20%) as a white solid. MS-ESI: [M+H]+ 530.3. 1H NMR (500 MHz, DMSO-d6) δ 8.56 (d, J=5.0 Hz, 1H), 8.53 (d, J=2.0 Hz, 1H), 8.21 (s, 1H), 8.03 (d, J=2.5 Hz, 1H), 7.89 (s, 1H), 7.78-7.5 (m, 1H), 7.51-7.48 (m, 2H), 7.39 (d, J=2.5 Hz, 1H), 6.07 (d, J=2.0 Hz, 1H), 4.91 (s, 1H), 4.42 (s, 2H), 3.71 (s, 3H), 3.58 (s, 3H), 1.39 (s, 9H)

Workup

  1. concentrationconcentrated under reduced pressure
  2. additionThe residue was diluted with dichloromethane (20 mL) and water (10 mL)
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with dichloromethane (3×15 mL)
  5. washThe combined organic layer was washed with brine
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-12e76eb096cf49be92d6413fc3c56a18
Source dataset
uspto-grants-2014_06
Patent number
US08754077B2

Reaction notes

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