Triethylamine → 1-Acetyl-6-bromo-2-({3-[4-(trifluoroacetyl)piperazin-1-yl]azetidin-1-yl}carbonyl)-1,2,3,4-tetrahydroquinoline

HRID 1023072Notes

Reaction equation

HRID 1023072 reaction equation
[NH:1]1[CH2:4][CH:3]([N:5]2[CH2:10][CH2:9][N:8]([C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])[CH2:7][CH2:6]2)[CH2:2]1.[C:17]([N:20]1[C:29]2[C:24](=[CH:25][C:26]([Br:30])=[CH:27][CH:28]=2)[CH2:23][CH2:22][CH:21]1[C:31](O)=[O:32])(=[O:19])[CH3:18].CCN(CC)CC.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[C:17]([N:20]1[C:29]2[C:24](=[CH:25][C:26]([Br:30])=[CH:27][CH:28]=2)[CH2:23][CH2:22][CH:21]1[C:31]([N:1]1[CH2:2][CH:3]([N:5]2[CH2:6][CH2:7][N:8]([C:11](=[O:16])[C:12]([F:13])([F:14])[F:15])[CH2:9][CH2:10]2)[CH2:4]1)=[O:32])(=[O:19])[CH3:18]

Participants

6

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 596256781-(4-Azetidin-3-yl-piperazin-1-yl)-2,2,2-trifluoro-ethanoneHCID 596259471-Acetyl-6-bromo-1,2,3,4-tetrahydroquinoline-2-carboxylic acid

Product 1

HCID 596259251-Acetyl-6-bromo-2-({3-[4-(trifluoroacetyl)piperazin-1-yl]azetidin-1-yl}carbonyl)-1,2,3,4-tetrahydroquinolineYield 69.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of compound 1g (228 mg, 0.74 mmol), compound 25c (22 mg, 0.74 mmol), and Et3N (0.3 mL, 2.22 mmol) in CH2Cl2 (7 mL) was added HATU (338 mg, 0.89 mmol). The reaction mixture was stirred at room temperature for 18 h. The resultant mixture was diluted with CH2Cl2 and washed with aqueous NaHCO3. The organic phase was dried over Na2SO4, filtered, and concentrated under reduced pressure. Purification of the residue by flash column chromatography (silica gel, 2% MeOH/EtOAc+0.5% Et3N) gave compound 25d (265 mg). LC/MS m/z (M+H+), 517.0 (M+2H+), 519.0.

Workup

  1. washwashed with aqueous NaHCO3
  2. dry with materialThe organic phase was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customPurification of the residue by flash column chromatography (silica gel, 2% MeOH/EtOAc+0.5% Et3N)

Sources & evidence

ORD record
ord-74bc3410ea734a3dbedd1b79f267c7d5
Source dataset
uspto-grants-2014_05
Patent number
US08722658B2

Reaction notes

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