Ethylamine → HCID 178465147, compound

HRID 518607Notes

Reaction equation

HRID 518607 reaction equation
[F:1][C:2]1[CH:35]=[CH:34][C:5]([C:6](/[N:8]=[C:9]2\[NH:10][C:11]3[CH:26]=[CH:25][C:24]([CH2:27][N:28]4[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]4)=[CH:23][C:12]=3[N:13]\2[C@@H:14]2[CH2:19][CH2:18][C@H:17]([C:20]([OH:22])=O)[CH2:16][CH2:15]2)=[O:7])=[CH:4][CH:3]=1.S(Cl)(Cl)=O.[CH2:40]([NH2:42])[CH3:41]>O.C(Cl)Cl>[CH2:40]([NH:42][C:20]([C@@H:17]1[CH2:16][CH2:15][C@H:14]([N:13]2[C:12]3[CH:23]=[C:24]([CH2:27][N:28]4[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]4)[CH:25]=[CH:26][C:11]=3[NH:10]/[C:9]/2=[N:8]\[C:6](=[O:7])[C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:35][CH:34]=2)[CH2:19][CH2:18]1)=[O:22])[CH3:41]

Participants

6

Reactant 3

HCID 6341EthylamineHCID 24386Thionyl ChlorideHCID 178522614HCID 178522614, compound

Product 1

HCID 178465147HCID 178465147, compoundYield 95.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

cis-4-((E)-2-(4-Fluorobenzoylimino)-6-(piperidin-1-ylmethyl)-2,3-dihydro-1H-benzo[d]imidazol-1-yl)cyclohexanecarboxylic acid (0.025 g, 0.052 mmol) was cooled to 0° C. under nitrogen. To this mixture was added thionyl chloride (0.381 mL, 5.22 mmol), and the resulting reaction mixture was stirred for 10 minutes. The mixture was concentrated under reduced pressure and dried under high vacuum. The residue was suspended in THF (0.5 mL) and cooled to 0° C. under a nitrogen atmosphere. To this mixture was added ethanamine (2M in THF) (0.059 mL, 1.045 mmol) dropwise, and the reaction was stirred at 0° C. for 30 minutes. The reaction mixture was diluted with water (10 mL) and DCM (20 mL), and the layers were separated. The organic phase was dried over sodium sulfate, filtered, and solvent was concentrated under reduced pressure to afford (E)-N-(1-(cis-4-(ethylcarbamoyl)cyclohexyl)-6-(piperidin-1-ylmethyl)-1H-benzo[d]imidazol-2(3H)-ylidene)-4-fluorobenzamide (0.025 g, 95% yield). MS m/z=506.2 [M+H]. Calc'd for C29H36FN5O2: 505.3. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.14 (t, J=7.19 Hz, 3H) 1.42-1.50 (m, 2H) 1.50-1.63 (m, 4H) 1.63-1.89 (m, 4H) 2.14-2.28 (m, 2H) 2.32-2.47 (m, 4H) 2.57-2.66 (m, 1H) 2.67-2.89 (m, 2H) 3.21-3.32 (m, 2H) 3.56 (s, 2H) 4.77-5.03 (m, 1H) 7.17-7.23 (m, 1H) 7.25-7.35 (m, 2H) 7.53 (d, J=8.12 Hz, 1H) 7.63 (s, 1H) 7.83-7.94 (m, 1H) 8.29-8.43 (m, 2H) 12.79 (s, 1H).

Workup

  1. customthe resulting reaction mixture
  2. concentrationThe mixture was concentrated under reduced pressure
  3. customdried under high vacuum
  4. stirringthe reaction was stirred at 0° C. for 30 minutes
  5. customthe layers were separated
  6. dry with materialThe organic phase was dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationsolvent was concentrated under reduced pressure

Sources & evidence

ORD record
ord-2349098503c14d49a5362e908ec573e0
Source dataset
uspto-grants-2015_08
Patent number
US09115127B2

Reaction notes

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