Lithium diisopropylamide → methyl 2-(tert-butoxy)-2-(4-(4-chlorophenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetate

HRID 1473191Notes

Reaction equation

HRID 1473191 reaction equation
C([N:8]1[C:12]2[C:13](=[O:35])[N:14]([CH3:34])[C:15]([CH:24]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[C:25]([O:27][CH3:28])=[O:26])=[C:16]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=3)[C:11]=2[CH:10]=[CH:9]1)C1C=CC=CC=1.[Li+].CC([N-]C(C)C)C>O1CCCC1>[C:30]([O:29][CH:24]([C:15]1[N:14]([CH3:34])[C:13](=[O:35])[C:12]2[NH:8][CH:9]=[CH:10][C:11]=2[C:16]=1[C:17]1[CH:18]=[CH:19][C:20]([Cl:23])=[CH:21][CH:22]=1)[C:25]([O:27][CH3:28])=[O:26])([CH3:33])([CH3:31])[CH3:32]

Participants

4

Reactant 2

HCID 2724682Lithium diisopropylamideHCID 89462902methyl 2-(1-benzyl-4-(4-chlorophenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)-2-(tert-butoxy)acetate

Product 1

HCID 89463134methyl 2-(tert-butoxy)-2-(4-(4-chlorophenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetateYield 63%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A 0° C. solution of methyl 2-(1-benzyl-4-(4-chlorophenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)-2-(tert-butoxy)acetate (400 mg, 0.811 mmol) in Tetrahydrofuran (THF) (6 mL) was slowly treated with LDA (2.0 M solution in tetrahydrofuran/heptanes/ethylbenzene) (0.811 mL, 1.623 mmol) and the mixture was allowed to stir at 0° C. for 20 min. The mixture was quenched with HCl (1M) and extracted with Ethyl acetate. The combined extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified on silica gel (0-10% Methanol/DCM) to afford methyl 2-(tert-butoxy)-2-(4-(4-chlorophenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetate (205 mg, 0.511 mmol, 63% yield) as a pale yellow solid. 1H NMR (400 MHz, CHLOROFORM-d) ppm 9.46 (s, 1H), 7.50-7.46 (m, 2H), 7.45-7.38 (m, 2H), 7.21-7.19 (m, 1H), 6.10-6.05 (m, 1H), 3.84-3.82 (s, 3H), 3.73-3.71 (s, 3H), 0.96 (s, 9H); LCMS (m/z) ES+=403 (M+1).

Workup

  1. customThe mixture was quenched with HCl (1M)
  2. extractionextracted with Ethyl acetate
  3. washThe combined extracts were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified on silica gel (0-10% Methanol/DCM)

Sources & evidence

ORD record
ord-d20fbdbeaa6f4ff8934a370997fd0892
Source dataset
uspto-grants-2015_04
Patent number
US09012642B2

Reaction notes

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