Triethylamine → HCID 46175650, compound

HRID 455987Notes

Reaction equation

HRID 455987 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:18][C:19]([F:22])([F:21])[F:20])=[C:6]2[C:10]=1[N:9]([CH2:11][CH2:12][O:13][CH3:14])[CH:8]=[C:7]2[C:15](O)=[O:16].CCN(CC)CC.Cl.[F:31][C:32]([F:51])([F:50])[C:33]([NH:35][CH2:36][C:37]1[CH:42]=[CH:41][C:40]([F:43])=[C:39]([CH:44]2[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]2)[CH:38]=1)=[O:34].CCN=C=NCCCN(C)C>C(Cl)Cl>[F:51][C:32]([F:50])([F:31])[C:33]([NH:35][CH2:36][C:37]1[CH:42]=[CH:41][C:40]([F:43])=[C:39]([CH:44]2[CH2:49][CH2:48][N:47]([C:15]([C:7]3[C:6]4[C:10](=[C:2]([F:1])[CH:3]=[CH:4][C:5]=4[O:18][C:19]([F:22])([F:20])[F:21])[N:9]([CH2:11][CH2:12][O:13][CH3:14])[CH:8]=3)=[O:16])[CH2:46][CH2:45]2)[CH:38]=1)=[O:34]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 46175555HCID 46175555, compoundHCID 461756497-Fluoro-1-(2-methoxy-ethyl)-4-trifluoromethoxy-1H-indole-3-carboxylic acid

Product 1

HCID 46175650HCID 46175650, compoundYield 99.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 8 (19.1 g, 59.6 mmol), Et3N (24.8 mL, 177.9 mmol), 2,2,2-trifluoro-N-(4-fluoro-3-piperidin-4-yl-benzyl)-acetamide hydrochloride (11, 26.4 g, 77.5 mmol) (14), and EDCI (17.1 g, 89.3 mmol) in CH2Cl2 is stirred at rt overnight. Both TLC and LC/MS indicate that the reaction is completed. The mixture is partitioned between H2O and CH2Cl2. The two layers are separated, and the organic layer is washed with brine, dried over MgSO4, filtered, and concentrated in vacuo. The crude material is purified on silica gel with heptane/EtOAc (40/60 to 0/100) as eluant to give 9 (36 g, 99%) as a white foam. 1H NMR (CDCl3) δ 7.37 (s, 1H), 7.20-7.10 (m, 2H), 7.10-6.85 (m, 4H), 4.95 (br s, 1H), 4.60-4.35 (m, 4H), 3.90 (br s, 1H), 3.73 (t, J=5.0 Hz, 2H), 3.32 (s, 3H), 3.25-2.70 (m, 3H), 2.05-1.50(m, 4H); 19F NMR (CDCl3) δ −57.54 (s, 3F), −75.39 (s, 3F), −119.31 (s, 1F), −134.96 (d, J=11.3 Hz, 1F); MS 608 (M+1, 100%).

Workup

  1. customThe mixture is partitioned between H2O and CH2Cl2
  2. customThe two layers are separated
  3. washthe organic layer is washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude material is purified on silica gel with heptane/EtOAc (40/60 to 0/100) as eluant

Sources & evidence

ORD record
ord-ad21f3317b864ec6beb25fbed7da793f
Source dataset
uspto-grants-2013_07
Patent number
US08497379B2

Reaction notes

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