Potassium bis(trimethylsilyl)amide → HCID 86574196, compound

HRID 1473229Notes

Reaction equation

HRID 1473229 reaction equation
C([N:8]1[C:12]2[C:13](=[O:38])[N:14]([CH3:37])[C:15]([CH:28]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[C:29]([OH:31])=[O:30])=[C:16]([C:17]3[C:18]([CH3:27])=[C:19]4[C:24](=[CH:25][CH:26]=3)[O:23][CH2:22][CH2:21][CH2:20]4)[C:11]=2[CH:10]=[CH:9]1)C1C=CC=CC=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+]>O1CCCC1>[C:33]([O:32][CH:28]([C:15]1[N:14]([CH3:37])[C:13](=[O:38])[C:12]2[NH:8][CH:9]=[CH:10][C:11]=2[C:16]=1[C:17]1[C:18]([CH3:27])=[C:19]2[C:24](=[CH:25][CH:26]=1)[O:23][CH2:22][CH2:21][CH2:20]2)[C:29]([OH:31])=[O:30])([CH3:36])([CH3:35])[CH3:34]

Participants

4

Reactant 2

HCID 3251421Potassium bis(trimethylsilyl)amide2×HCID 71537362HCID 71537362, compound

Product 1

HCID 86574196HCID 86574196, compoundYield 94.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

An ice cold solution of 2-(1-benzyl-6-methyl-4-(5-methylchroman-6-yl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)-2-(tert-butoxy)acetic acid (210 mg, 0.408 mmol) in Tetrahydrofuran (THF) (3 mL) was treated with KHMDS (8.16 mL, 4.08 mmol) and then heated to 50° C. for 2 hours. Additional KHMDS (8.16 mL, 4.08 mmol) was added and the mixture was stirred at 70° C. overnight. The mixture was quenched with HCl (1M) at 0° C. and extracted with ethyl acetate. The combined extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by reverse phase chromatography (10-90% MeCN/H2O-0.1% TFA, 12 min) to afford 2-(tert-butoxy)-2-(6-methyl-4-(5-methylchroman-6-yl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetic acid (163 mg, 0.384 mmol, 94% yield) as white solid. 1H NMR (400 MHz, CHLOROFORM-d) ppm 11.20-11.38 (m, 1H) 7.28-7.40 (m, 1H) 6.93-7.05 (m, 1H) 6.70-6.82 (m, 1H) 5.84-6.01 (m, 1H) 5.25-5.57 (m, 1H) 4.15-4.28 (m, 2H) 3.74-3.90 (m, 3H) 2.61-2.78 (m, 2H) 2.04-2.19 (m, 2H) 1.87-2.06 (m, 2H) 0.94-1.26 (m, 9H); LCMS (m/z) ES+=425 (M+1).

Workup

  1. customThe mixture was quenched with HCl (1M) at 0° C.
  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 by reverse phase chromatography (10-90% MeCN/H2O-0.1% TFA, 12 min)

Sources & evidence

ORD record
ord-8cd3dd5ca4744de1a9e82d45b76eed81
Source dataset
uspto-grants-2015_04
Patent number
US09012642B2

Reaction notes

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