Lithium Hydroxide → HCID 71537935, compound

HRID 1473225Notes

Reaction equation

HRID 1473225 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:35])[CH2:10][N:11]2[C:15]3[C:16](=[O:34])[N:17]([CH3:33])[C:18]([CH:27]([OH:32])[C:28]([O:30]C)=[O:29])=[C:19]([C:20]4[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][CH:21]=4)[C:14]=3[CH:13]=[CH:12]2)=[CH:4][CH:3]=1.Cl(O)(=O)(=O)=O.[Li+].[OH-]>C(OC(C)(C)C)(=O)C.O1CCCC1>[C:14]([O:32][CH:27]([C:18]1[N:17]([CH3:33])[C:16](=[O:34])[C:15]2[N:11]([CH2:10][C:9]([NH:8][C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)=[O:35])[CH:12]=[CH:13][C:14]=2[C:19]=1[C:20]1[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][CH:21]=1)[C:28]([OH:30])=[O:29])([CH3:19])([CH3:15])[CH3:13]

Participants

6

Reactant 3

HCID 3939Lithium HydroxideHCID 24247Perchloric AcidHCID 89462643HCID 89462643, compound

Product 1

HCID 71537935HCID 71537935, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 10908tert-Butyl acetateSolvent

Procedure

An ice cold mixture of methyl 2-(1-(2-((4-fluorophenyl)amino)-2-oxoethyl)-6-methyl-7-oxo-4-(p-tolyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)-2-hydroxyacetate (20.5 mg, 0.043 mmol) in t-Butyl acetate (5.0 mL) was treated with perchloric acid (0.2 mL, 0.102 mmol) and then stirred at ambient temperature for 2 hours. The mixture was quenched with 3M NaOH and extracted with ethyl acetate. The combined extracts were washed with brine, dried over sodium sulfate filtered and concentrated. The residue was dissolved in Methanol (1.000 mL) and Tetrahydrofuran (THF) (1.000 mL), treated with 1N LiOH (0.4 mL, 0.400 mmol) and then heated to 70° C. for 80 minutes. The mixture was concentrated and then purified by reverse phase chromatography (10-90% MeCN/H2O-0.1% TFA, 12 min) to give the desired product as a light brown residue. 1H NMR (400 MHz, CHLOROFORM-d) ppm 10.54 (s, 1H), 7.62-7.44 (m, 3H), 7.36-7.14 (m, 4H), 7.07-6.91 (m, 2H), 6.09 (d, J=2.9 Hz, 1H), 5.50 (s, 1H), 5.22-5.16 (m, 1H), 5.15-5.08 (m, 1H), 3.76 (s, 3H), 2.44 (s, 3H), 1.00 (s, 9H); LC/MS (m/z) ES+=520 (M+1).

Workup

  1. customThe mixture was quenched with 3M NaOH
  2. extractionextracted with ethyl acetate
  3. washThe combined extracts were washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved in Methanol (1.000 mL)
  8. temperatureheated to 70° C. for 80 minutes
  9. concentrationThe mixture was concentrated
  10. custompurified by reverse phase chromatography (10-90% MeCN/H2O-0.1% TFA, 12 min)

Sources & evidence

ORD record
ord-8ef69a4b2f374599b542c88d7ef77bc6
Source dataset
uspto-grants-2015_04
Patent number
US09012642B2

Reaction notes

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