Cyclohexanecarboxylic acid → HCID 58415950, compound

HRID 1943035Notes

Reaction equation

HRID 1943035 reaction equation
[F:1][C:2]1([F:30])[CH2:7][CH2:6][N:5]([CH:8]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:9][NH:10][CH2:11][C:12]2[C:13](=[O:23])[N:14]([CH3:22])[C:15]3[C:20]([CH:21]=2)=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH2:4][CH2:3]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH:55]1([C:61](O)=[O:62])[CH2:60][CH2:59][CH2:58][CH2:57][CH2:56]1.CCN(C(C)C)C(C)C>CN(C=O)C>[F:30][C:2]1([F:1])[CH2:3][CH2:4][N:5]([CH:8]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:9][N:10]([CH2:11][C:12]2[C:13](=[O:23])[N:14]([CH3:22])[C:15]3[C:20]([CH:21]=2)=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:61]([CH:55]2[CH2:60][CH2:59][CH2:58][CH2:57][CH2:56]2)=[O:62])[CH2:6][CH2:7]1

Participants

6

Reactant 4

HCID 7413Cyclohexanecarboxylic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58415922HCID 58415922, compound

Product 1

HCID 58415950HCID 58415950, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

3-({[2-(4,4-difluoropiperidin-1-yl)-2-phenylethyl]amino}methyl)-1-methylquinolin-2(1H)-one (52 mg, 0.126 mmol), HATU (57.7 mg, 0.152 mmol), cyclohexanecarboxylic acid (0.019 ml, 0.152 mmol), and DIEA (0.026 ml, 0.152 mmol) were combined in DMF (1.5 ml) and the reaction heated at 50° C. for 0.75 hours. The mixture was purified directly by reversed-phase chromatography (15-95% ACN in water (with 0.5 ml/l NH4OH) over 20 min at 20 ml/min, 20×100 mm Phenomenex Gemini C18 column). Fractions containing desired material were concentrated in vacuo and repurified by reversed-phase chromatography (5-50% ACN (with 0.1% TFA) in water (with 0.1% TFA) over 20 min at 20 ml/min, 20×100 mm Phenomenex Gemini C18 column). Desired fractions were free-based via Phenomenex Strata X-C cartridge. HRMS [M+H] 1+ 522.2936. 1H NMR (400 MHz, CDCl3): δ 7.60-7.55 (m, 1 H), 7.53-7.49 (m, 1 H), 7.39 (d, J=8.52 Hz, 1 H), 7.35-7.28 (m, 4 H), 7.25-7.19 (m, 3 H), 4.50-4.35 (m, 2 H), 4.16-4.07 (m, 1 H), 3.88 (t, J=7.6 Hz, 1 H), 3.76 (s, 3 H), 3.31 (dd, J=7.38 Hz, 13.42 Hz, 1 H), 2.69-2.65 (m, 2 H), 2.53-2.43 (m, 2 H), 2.28-2.20 (m, 1 H), 2.01-1.88 (m, 4 H), 1.74-1.34 (m, 7 H), 1.25-1.05 (m, 3 H). 29.8 mg, 45%.

Workup

  1. customThe mixture was purified directly by reversed-phase chromatography (15-95% ACN in water (with 0.5 ml/l NH4OH) over 20 min at 20 ml/min, 20×100 mm Phenomenex Gemini C18 column)
  2. additionFractions containing desired material
  3. concentrationwere concentrated in vacuo
  4. customrepurified by reversed-phase chromatography (5-50% ACN (with 0.1% TFA) in water (with 0.1% TFA) over 20 min at 20 ml/min, 20×100 mm Phenomenex Gemini C18 column)

Sources & evidence

ORD record
ord-31e37584bae0443b835a58eaa6454425
Source dataset
uspto-grants-2013_03
Patent number
US08389720B2

Reaction notes

Loading…