1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → N-[(5-fluoro-1-methylindole-2-carbonyl)valinyl]-3-amino-4-hydroxy-5-fluoropentanoic acid, t-butyl ester

HRID 362493Notes

Reaction equation

HRID 362493 reaction equation
CCN=C=NCCCN(C)C.[F:12][C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[N:18]([CH3:22])[C:17]([C:23]([OH:25])=O)=[CH:16]2.[NH2:26][C@H:27]([C:31]([NH:33][CH:34]([CH:43]([OH:46])[CH2:44][F:45])[CH2:35][C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])=[O:32])[CH:28]([CH3:30])[CH3:29]>CN(C1C=CN=CC=1)C.CN(C=O)C>[F:12][C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[N:18]([CH3:22])[C:17]([C:23]([NH:26][C@H:27]([C:31]([NH:33][CH:34]([CH:43]([OH:46])[CH2:44][F:45])[CH2:35][C:36]([O:38][C:39]([CH3:40])([CH3:41])[CH3:42])=[O:37])=[O:32])[CH:28]([CH3:29])[CH3:30])=[O:25])=[CH:16]2

Participants

6

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 6625465-Fluoro-1-methyl-1H-indole-2-carboxylic acidHCID 86584005N-(valinyl)-3-amino-4-hydroxy-5-fluoropentanoic acid, t-butyl ester

Product 1

HCID 86585790N-[(5-fluoro-1-methylindole-2-carbonyl)valinyl]-3-amino-4-hydroxy-5-fluoropentanoic acid, t-butyl ester

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

DMAP (257 mg, 2.08 mmol) and EDAC (427 mg, 2.23 mmol) were added as solids to a solution of 5-fluoro-1-methylindole-2-carboxylic acid (359 mg, 86 mmol in 3 mL of DMF), and the resultant reaction mixture was stirred for 10 minutes under a nitrogen atmosphere at 0° C. N-(Valinyl)-3-amino-4-hydroxy-5-fluoropentanoic acid, t-butyl ester (579 mg, 1.86 mmol) in DMF (3 mL) was added and the resulting solution was stirred for 1 hour under a nitrogen atmosphere at 0° C. and 4 hours at room temperature. The reaction mixture was partitioned between ethyl acetate and 5% KHSO4 solution and the aqueous solution was back-extracted with ethyl acetate. The combined ethyl acetate solutions were washed with 5% KHSO4 solution, saturated sodium bicarbonate solution (2×) and brine, dried over sodium sulfate, and concentrated to give the title product as a slightly yellow solid (0.827 mg). TLC: (methanol/methylene chloride, 1:9): Rf =0.52.

Workup

  1. customthe resultant reaction mixture
  2. stirringthe resulting solution was stirred for 1 hour under a nitrogen atmosphere at 0° C. and 4 hours at room temperature
  3. customThe reaction mixture was partitioned between ethyl acetate and 5% KHSO4 solution
  4. extractionthe aqueous solution was back-extracted with ethyl acetate
  5. washThe combined ethyl acetate solutions were washed with 5% KHSO4 solution, saturated sodium bicarbonate solution (2×) and brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-c7aa2e9386d54e20868244cefd582719
Source dataset
uspto-grants-1999_02
Patent number
US05869519

Reaction notes

Loading…