Diisopropylamine → N-(2-Diethylaminoethyl)-2-[2-(2-(2,3-difluorophenyl)ethyl)-4-oxo-4H-quinolin-1-yl]-N-(4'-trifluoromethylbiphenyl-4-ylmethyl)acetamide

HRID 1768326Notes

Reaction equation

HRID 1768326 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:9][CH2:10][C:11]1[N:12]([CH2:22][C:23]([OH:25])=O)[C:13]2[C:18]([C:19](=[O:21])[CH:20]=1)=[CH:17][CH:16]=[CH:15][CH:14]=2.[CH2:26]([N:28]([CH2:49][CH3:50])[CH2:29][CH2:30][NH:31][CH2:32][C:33]1[CH:38]=[CH:37][C:36]([C:39]2[CH:44]=[CH:43][C:42]([C:45]([F:48])([F:47])[F:46])=[CH:41][CH:40]=2)=[CH:35][CH:34]=1)[CH3:27].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(NC(C)C)(C)C>ClCCl>[CH2:49]([N:28]([CH2:26][CH3:27])[CH2:29][CH2:30][N:31]([CH2:32][C:33]1[CH:38]=[CH:37][C:36]([C:39]2[CH:40]=[CH:41][C:42]([C:45]([F:46])([F:47])[F:48])=[CH:43][CH:44]=2)=[CH:35][CH:34]=1)[C:23](=[O:25])[CH2:22][N:12]1[C:13]2[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:19](=[O:21])[CH:20]=[C:11]1[CH2:10][CH2:9][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]([F:8])[C:2]=1[F:1])[CH3:50]

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11233414N,N-Diethyl-N'-(4'-trifluoromethylbiphenyl-4-ylmethyl)-ethane-1,2-diamineHCID 236143022-[2-(2-(2,3-difluorophenyl)ethyl)-4-oxo-4H-quinolin-1-yl]-acetic acid

Product 1

HCID 10211944N-(2-Diethylaminoethyl)-2-[2-(2-(2,3-difluorophenyl)ethyl)-4-oxo-4H-quinolin-1-yl]-N-(4'-trifluoromethylbiphenyl-4-ylmethyl)acetamideYield 93.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-[2-(2-(2,3-difluorophenyl)ethyl)-4-oxo-4H-quinolin-1-yl]-acetic acid (Int. E2) (0.26 g, 1 equiv), N,N-diethyl-N′-(4′-trifluoromethylbiphenyl-4-ylmethyl)ethane-1,2-diamine (Int. A2) (0.265 g, 1 equiv), HATU (0.28 g, 1.2 equiv) and diisopropylamine (0.32 ml, 2.4 equiv) in dichloromethane (15 ml) was stirred at room temperature overnight, then washed with aqueous ammonium chloride and aqueous sodium bicarbonate. The organic layer was dried and evaporated, and the product purified by column chromatography (silica, 2% [2M ammonia in methanol] in dichloromethane). Product fractions were evaporated to an off-white foam (0.201 g). Trituration with ether gave the title compound as a white solid (0.476 g). 1H-NMR (d6-DMSO, ca 2:1 rotamer mixture) δ 0.93 (6H, 2×t), 2.38–2.80 (4H, m), 2.90–3.05 (4H, m), 3.45 (2H, m), 4.30–4.95 (4H, m), 5.23–5.58 (2H, m), 6.06 (1H, 2×s), 7.14–7.38 (7H, m), 7.50–7.95 (7H, m), 8.16 (1H, m); MS (APCI+) found (M+1)=676. C39H38F5N3O2 requires 675.

Workup

  1. washwashed with aqueous ammonium chloride and aqueous sodium bicarbonate
  2. customThe organic layer was dried
  3. customevaporated
  4. customthe product purified by column chromatography (silica, 2% [2M ammonia in methanol] in dichloromethane)
  5. customProduct fractions were evaporated to an off-white foam (0.201 g)

Sources & evidence

ORD record
ord-70f5e09a1c214a8d99019cb466a3019d
Source dataset
uspto-grants-2007_06
Patent number
US07235566B2

Reaction notes

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