Proton sponge → HCID 60083663, compound

HRID 1883149Notes

Reaction equation

HRID 1883149 reaction equation
[C:1]([C@@H:3]([NH:6][C:7]([C@@H:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C@@H:10]1[NH:15][C:16]([C:18]1[N:19]([CH3:27])[C:20]2[C:25]([CH:26]=1)=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:17])=[O:8])[CH2:4][OH:5])#[N:2].F[B-](F)(F)F.[CH3:33][O+](C)C.CN(C1C2C(N(C)C)=CC=CC=2C=CC=1)C>ClCCl>[C:1]([C@@H:3]([NH:6][C:7]([C@@H:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C@@H:10]1[NH:15][C:16]([C:18]1[N:19]([CH3:27])[C:20]2[C:25]([CH:26]=1)=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:17])=[O:8])[CH2:4][O:5][CH3:33])#[N:2]

Participants

5

Reactant 3

HCID 88675Proton spongeHCID 2735153Oxonium, trimethyl-, tetrafluoroborate(1-) (1:1)HCID 60091030HCID 60091030, compound

Product 1

HCID 60083663HCID 60083663, compoundYield 38.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

N-[(1S,2R)-2-({[(1R)-1-Cyano-2-hydroxyethyl]amino}carbonyl)cyclohexyl]-1-methyl-1H-indole-2-carboxamide from Example 4 (0.20 g, 0.54 mmol) was dissolved in dichloromethane (8 mL), cooled to 0° C. under nitrogen in the dark, and stirred for 15 minutes. Trimethyloxonium tetrafluoroborate (0.10 g, 0.68 mmol) was added (Sowinski, J. A.; Toogood, P. L. J. Org. Chem. 1996, 61, 7671). After 20 minutes, proton sponge (0.14 g, 0.65 mmol) was added, and the reaction was allowed to warm to room temperature and was stirred for 21 hours. The reaction mixture was filtered through a pad of celite and the pad washed with dichloromethane. The filtrate was washed with 1M hydrochloric acid, brine, dried on magnesium sulfate, and concentrated. Purification by column chromatography (5:95 methanol:dichlormethane) gave 1-methyl-1H-indole-2-carboxylic acid {(1S,2R)-2-[((R)-cyano-methoxymethyl-methyl)-carbamoyl]-cyclohexyl}-amide (0.08 g, 38%). MS: 383 (M+H).

Workup

  1. waitAfter 20 minutes
  2. temperatureto warm to room temperature
  3. stirringwas stirred for 21 hours
  4. filtrationThe reaction mixture was filtered through a pad of celite
  5. washthe pad washed with dichloromethane
  6. washThe filtrate was washed with 1M hydrochloric acid, brine
  7. customdried on magnesium sulfate
  8. concentrationconcentrated
  9. customPurification by column chromatography (5:95 methanol:dichlormethane)

Sources & evidence

ORD record
ord-7b68b05b4de94ff6a7e4acc044e09be2
Source dataset
uspto-grants-2004_07
Patent number
US06759428B2

Reaction notes

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