1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 2-(S)-[(5-Chloro-1H-pyrrolo[2,3-b]pyridine-2-carbonyl)amino]-3-(4-fluorophenyl)-propionic acid tert-butyl ester

HRID 751738Notes

Reaction equation

HRID 751738 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[CH:10]=[C:9]([C:11]([OH:13])=O)[NH:8][C:5]2=[N:6][CH:7]=1.Cl.[C:15]([O:19][C:20](=[O:31])[C@@H:21]([NH2:30])[CH2:22][C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=1)([CH3:18])([CH3:17])[CH3:16].C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C>CN(C=O)C>[C:15]([O:19][C:20](=[O:31])[C@@H:21]([NH:30][C:11]([C:9]1[NH:8][C:5]2=[N:6][CH:7]=[C:2]([Cl:1])[CH:3]=[C:4]2[CH:10]=1)=[O:13])[CH2:22][C:23]1[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=1)([CH3:18])([CH3:16])[CH3:17]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 446307055-chloro-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acidHCID 67278629tert-butyl (2S)-2-amino-3-(4-fluorophenyl)propanoate hydrochloride

Product 1

HCID 597535552-(S)-[(5-Chloro-1H-pyrrolo[2,3-b]pyridine-2-carbonyl)amino]-3-(4-fluorophenyl)-propionic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-chloro-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid (Preparation 57, 500 mg, 2.54 mmol) in DMF (20 mL) was added 2-(S)-amino-3-(4-fluorophenyl)propionic acid tert-butyl ester hydrochloride (Preparation 114, 701 mg, 2.54 mmol), HOBt (344 mg, 2.54 mmol) and DIPEA (1.4 mL, 7.88 mmol). After 5 min, EDCI (634 mg, 3.31 mmol) was added and the reaction mixture stirred at rt for 72 h. The solvent was removed in vacuo and the solid partitioned between water (50 mL) and ethyl acetate (3×40 mL). The combined organic phase was washed with brine (20 mL), dried (MgSO4), concentrated in vacuo and purified by chromatography on silica gel eluting with methanol:dichloromethane (1:99) to give the title compound. δH (CD3OD): 1.42 (9H, s), 3.09 (1H, dd), 3.22 (1H, dd), 4.76 (1H, m), 6.98 (2H, m), 7.07 (1H, s), 7.27 (2H, m), 8.06 (1H, d), 8.28 (1H, d); m/z (ES+)=418 [M+H]+.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe solid partitioned between water (50 mL) and ethyl acetate (3×40 mL)
  3. washThe combined organic phase was washed with brine (20 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. custompurified by chromatography on silica gel eluting with methanol:dichloromethane (1:99)

Sources & evidence

ORD record
ord-a9dd74c143124cabbe5902b85f8b2776
Source dataset
uspto-grants-2008_07
Patent number
US07405210B2

Reaction notes

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