Triethylamine → 3-(4-Fluorophenyl)-6-({3-[4-(1,3-thiazol-2-ylcarbonyl)piperazin-1-yl]azetidin-1-yl}carbonyl)-1H-indole

HRID 2365662Notes

Reaction equation

HRID 2365662 reaction equation
[NH:1]1[CH2:4][CH:3]([N:5]2[CH2:10][CH2:9][N:8]([C:11]([C:13]3[S:14][CH:15]=[CH:16][N:17]=3)=[O:12])[CH2:7][CH2:6]2)[CH2:2]1.[F:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2[C:33]3[C:28](=[CH:29][C:30]([C:34](O)=[O:35])=[CH:31][CH:32]=3)[NH:27][CH:26]=2)=[CH:21][CH:20]=1.CCN(CC)CC.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl.O>[F:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2[C:33]3[C:28](=[CH:29][C:30]([C:34]([N:1]4[CH2:2][CH:3]([N:5]5[CH2:6][CH2:7][N:8]([C:11]([C:13]6[S:14][CH:15]=[CH:16][N:17]=6)=[O:12])[CH2:9][CH2:10]5)[CH2:4]4)=[O:35])=[CH:31][CH:32]=3)[NH:27][CH:26]=2)=[CH:21][CH:20]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59625677(4-(Azetidin-3-yl)piperazin-1-yl)(thiazol-2-yl)methanoneHCID 596260093-(4-fluorophenyl)-1H-indole-6-carboxylic acid

Product 1

HCID 596260003-(4-Fluorophenyl)-6-({3-[4-(1,3-thiazol-2-ylcarbonyl)piperazin-1-yl]azetidin-1-yl}carbonyl)-1H-indoleYield 77.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a mixture of compound 5e (42.9 mg, 0.132 mmol), compound 53e (30.6 mg, 0.12 mmol), and Et3N (0.084 mL, 0.6 mmol) in CH2Cl2 (1 mL) at room temperature was added HATU (70 mg, 0.168 mmol). The reaction mixture was stirred at room temperature overnight. The mixture was diluted with CH2Cl2 and H2O, washed with aq. NaHCO3 and brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by flash column chromatography (silica gel, 2-4% MeOH/EtOAc) to give Cpd 1317 (45.4 mg). 1H NMR (400 MHz, CDCl3): δ 8.56 (br. s., 1H), 7.83-7.94 (m, 3H), 7.57-7.65 (m, 2H), 7.55 (d, J=3.2 Hz, 1H), 7.46 (d, J=2.4 Hz, 1H), 7.40-7.45 (m, 1H), 7.13-7.20 (m, 2H), 4.07-4.66 (m, 6H), 3.76-4.01 (m, 2H), 3.21-3.36 (m, 1H), 2.38-2.64 (m, 4H). MS m/z (M+H+) 490.2.

Workup

  1. washwashed with aq. NaHCO3 and brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by flash column chromatography (silica gel, 2-4% MeOH/EtOAc)

Sources & evidence

ORD record
ord-ec01de0c26984ee0a35b8056c984a02f
Source dataset
uspto-grants-2014_04
Patent number
US08697683B2

Reaction notes

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