1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → N-(5-Fluoro-pyridin-2-ylmethyl)-4-(3-phenyl-indole-1-sulfonyl)-benzamide

HRID 737049Notes

Reaction equation

HRID 737049 reaction equation
[C:1]1([C:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[N:9]([S:16]([C:19]3[CH:27]=[CH:26][C:22]([C:23](O)=[O:24])=[CH:21][CH:20]=3)(=[O:18])=[O:17])[CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:28][CH2:29][C:30]1[CH:35]=[CH:34][C:33]([F:36])=[CH:32][N:31]=1.CCN=C=NCCCN(C)C>C(Cl)Cl.CN(C1C=CN=CC=1)C>[F:36][C:33]1[CH:34]=[CH:35][C:30]([CH2:29][NH:28][C:23](=[O:24])[C:22]2[CH:21]=[CH:20][C:19]([S:16]([N:9]3[C:10]4[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=4)[C:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)=[CH:8]3)(=[O:18])=[O:17])=[CH:27][CH:26]=2)=[N:31][CH:32]=1

Participants

6

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 45079543(5-Fluoropyridin-2-yl)methanamineHCID 589751414-(3-Phenyl-indole-1-sulfonyl)-benzoic acid

Product 1

HCID 58975149N-(5-Fluoro-pyridin-2-ylmethyl)-4-(3-phenyl-indole-1-sulfonyl)-benzamide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

Add to a stirring mixture of 4-(3-phenyl-indole-1-sulfonyl)-benzoic acid (5.0 g, 13.25 mmol) and 2-aminomethyl-5-fluoropyridine (dihydrochloride) (2.9 g, 14.57 mmol) in anhydrous methylene chloride (60 mL), EDCI (3.8 g, 19.82 mmol) and 4-DMAP (6.0 g, 49.10 mmol). Stir the resulting solution overnight at room temperature, concentrate to a paste, and partition between ethyl acetate (100 mL), water (100 mL), and brine (100 mL). Dry the organic layer over sodium sulfate and concentrate to an oil. Dissolve the oil in methylene chloride and add to a biotage 65 cartridge. Elute with 1:1 ethyl acetate/hexanes to provide isolation of the pure 3 (N-(5-Fluoro-pyridin-2-ylmethyl)-4-(3-phenyl-indole-1-sulfonyl)-benzamide as a solid, 5.7 g (89%): 1H NMR (DMSO-d6) δ 9.32 (t, J=5.9 Hz, 1H), 8.46 (d, J=2.9 Hz, 1H), 8.20 (d, J=8.3 Hz, 2H), 8.12 (s, 1H), 8.03 (m, 3H), 7.82 (d, J=7.8 Hz, 1H), 7.72 (d, J=6.8 Hz, 2H), 7.62 (dt, J=2.9, 8.8 Hz, 1H), 7.50 (t, J=7.3 Hz, 2H), 7.39 (m, 4H), 4.50 (d, J=5.9 Hz, 2H); MS (ESI) m/z 486 (m+H).

Workup

  1. concentrationconcentrate to a paste
  2. custompartition between ethyl acetate (100 mL), water (100 mL), and brine (100 mL)
  3. dry with materialDry the organic layer over sodium sulfate
  4. concentrationconcentrate to an oil
  5. dissolutionDissolve the oil in methylene chloride
  6. additionadd to a biotage 65 cartridge
  7. washElute with 1:1 ethyl acetate/hexanes

Sources & evidence

ORD record
ord-f0b2448fa602418f8b28e7ef2b9fc7fb
Source dataset
uspto-grants-2009_09
Patent number
US07595339B2

Reaction notes

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