Triethylamine → HCID 66853365, compound

HRID 1406426Notes

Reaction equation

HRID 1406426 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=[C:9]1[C:17]1[C:18](=[O:32])[N:19]([CH2:24]OCC[Si](C)(C)C)[CH:20]=[C:21]([NH2:23])[CH:22]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[C:40]1([C@@H:46]([N:48]2[CH:52]=[C:51]([C:53](Cl)=[O:54])[CH:50]=[N:49]2)[CH3:47])[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>ClCCl>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:10]=[C:9]1[C:17]1[C:18](=[O:32])[N:19]([CH3:24])[CH:20]=[C:21]([NH:23][C:53]([C:51]2[CH:50]=[N:49][N:48]([C@H:46]([C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[CH3:47])[CH:52]=2)=[O:54])[CH:22]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 58117230HCID 58117230, compoundHCID 58117448HCID 58117448, compound2×

Product 1

HCID 66853365HCID 66853365, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
5 °C

Procedure

Intermediate (6c), 2-[5-Amino-2-oxo-1-(2-trimethylsilanyl-ethoxymethyl)-1,2-dihydro-pyridin-3-yl]-indole-1-carboxylic acid tert-butyl ester (100 mg, 0.22 mmol) was stirred in dichloromethane (5 mL) at RT with triethylamine (0.092 mL, 0.66 mmol). The reaction mixture was cooled to 5° C. and then a solution of intermediate (6h), 1-((S)-1-Phenyl-ethyl)-1H-pyrazole-4-carbonyl chloride, (54 mg, 0.231 mmol) in dichloromethane (1 mL) was added drop wise. After addition the reaction was stirred at RT for 1 hour and then the reaction mixture was concentrated in vacuo and the residue partitioned between ethyl acetate (10 mL) and aqueous saturated sodium hydrogen carbonate solution (10 mL). The organic layer was separated and the aqueous was extracted with a further portion of ethyl acetate (10 mL). The combined ethyl acetate layers were washed with brine, dried (Na2SO4) and concentrated in vacuo. The resultant crude product was purified by flash chromatography on SiO2 eluting with hexane—50% ethyl acetate/hexane (gradient) to afford the desired intermediate, 2-(1-Methyl-2-oxo-5-{[1-((S)-1-phenyl-ethyl)-1H-pyrazole-4-carbonyl]-amino}-1,2-dihydro-pyridin-3-yl)-indole-1-carboxylic acid tert-butyl ester, 0.108 g, 76%.

Workup

  1. additionAfter addition the reaction
  2. concentrationthe reaction mixture was concentrated in vacuo
  3. customthe residue partitioned between ethyl acetate (10 mL) and aqueous saturated sodium hydrogen carbonate solution (10 mL)
  4. customThe organic layer was separated
  5. extractionthe aqueous was extracted with a further portion of ethyl acetate (10 mL)
  6. washThe combined ethyl acetate layers were washed with brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customThe resultant crude product was purified by flash chromatography on SiO2 eluting with hexane—50% ethyl acetate/hexane (gradient)

Sources & evidence

ORD record
ord-10b52694c2b0459a80d8dec339ce9531
Source dataset
uspto-grants-2014_12
Patent number
US08916591B2

Reaction notes

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