Hydrochloric Acid → HCID 20740209, compound

HRID 1883137Notes

Reaction equation

HRID 1883137 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]1[C:11]([NH:13][C@H:14]1[CH2:19][CH2:18][CH2:17][CH2:16][C@H:15]1[C:20]([NH:22][C@@H:23]([CH2:27][CH2:28][C:29]([NH2:31])=O)[C:24]([NH2:26])=O)=[O:21])=[O:12].FC(F)(F)C(OC(=O)C(F)(F)F)=O.Cl>N1C=CC=CC=1.C(Cl)Cl>[C:24]([CH:23]([NH:22][C:20]([C@@H:15]1[CH2:16][CH2:17][CH2:18][CH2:19][C@@H:14]1[NH:13][C:11]([C:3]1[N:2]([CH3:1])[C:10]2[C:5]([CH:4]=1)=[CH:6][CH:7]=[CH:8][CH:9]=2)=[O:12])=[O:21])[CH2:27][CH2:28][C:29]#[N:31])#[N:26]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 9845Trifluoroacetic anhydrideHCID 60083612HCID 60083612, compound

Product 1

HCID 20740209HCID 20740209, compoundYield 91.5%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a 0° C. suspension of (S)-2-({(1R,2S)-2-[(1-Methyl-1H-indole-2-carbonyl)-amino]-cyclohexanecarbonyl}-amino)-pentanedioic acid diamide (0.53 g, 1.2 mmol) in 30 mL of anhydrous pyridine and 30 mL of CH2Cl2 was slowly added trifluoroacetic anhydride dropwise. The resulting yellow reaction mixture was stirred at 0° C. for 15 min, and poured into a slurry of ice and a 1N HCl solution. The mixture was extracted with 250 mL of ethyl acetate, washed with a 1N solution of HCl (3×250 mL), water (250 mL), and dried with sodium sulfate, filtered, concentrated and purified by column chromatography (5:95, MeOH/CH2Cl2) to give 430 mg (89%) of 1-methyl-1H-indole-2-carboxylic acid [(1S,2R)-2-(1,3-dicyano-propylcarbamoyl)-cyclohexyl]-amide as a light-yellow liquid, which was determined to be a 38:62 ratio of epimers by 1H NMR spectroscopy. MS: 392 (M+H+).

Workup

  1. additionpoured into a slurry of ice
  2. extractionThe mixture was extracted with 250 mL of ethyl acetate
  3. washwashed with a 1N solution of HCl (3×250 mL), water (250 mL)
  4. dry with materialdried with sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by column chromatography (5:95, MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-bbe1a8d533ee4f3c891ea9b12b36bb7a
Source dataset
uspto-grants-2004_07
Patent number
US06759428B2

Reaction notes

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