Triethylamine → HCID 178490071, compound

HRID 1028563Notes

Reaction equation

HRID 1028563 reaction equation
[F:1][C:2]([F:41])([F:40])[C:3]1[CH:4]=[C:5]([C@@H:13]([NH2:39])[C@@H:14]([NH:16][CH2:17][C:18]2[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[CH:20][C:19]=2[C:28]2[CH:33]=[C:32]([CH:34]([CH3:36])[CH3:35])[CH:31]=[CH:30][C:29]=2[O:37][CH3:38])[CH3:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C(N(CC)CC)C.C1C=CC(O[C:56](OC2C=CC=CC=2)=[N:57][C:58]#[N:59])=CC=1>ClC(Cl)C>[F:1][C:2]([F:40])([F:41])[C:3]1[CH:4]=[C:5]([C@@H:13]2[C@H:14]([CH3:15])[N:16]([CH2:17][C:18]3[CH:23]=[C:22]([C:24]([F:25])([F:26])[F:27])[CH:21]=[CH:20][C:19]=3[C:28]3[CH:33]=[C:32]([CH:34]([CH3:35])[CH3:36])[CH:31]=[CH:30][C:29]=3[O:37][CH3:38])[C:56](=[N:57][C:58]#[N:59])[NH:39]2)[CH:6]=[C:7]([C:9]([F:11])([F:10])[F:12])[CH:8]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 688090Diphenyl N-CyanocarbonimidateHCID 59135060(1R,2S)-1-[3,5-bis(trifluoromethyl)phenyl]-N2-{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}propane-1,2-diamine

Product 1

HCID 178490071HCID 178490071, compound

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of (1R,2S)-1-[3,5-bis(trifluoromethyl)phenyl]-N2-{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}propane-1,2-diamine (25.1 mg, 0.0424 mmol) in dichloroethane (1.5 mL) was added triethylamine (15 μL, 0.105 mmol) and diphenyl cyanocarbonimidate (13 mg, 0.053 mmol). The reaction was heated at 60° C. overnight, cooled to room temperature, filtered, and loaded directly onto a silica gel column for purification by flash chromatography with 10 to 40% EtOAc/hexanes to afford ((4R,5S)-4-[3,5-bis(trifluoromethyl)phenyl]-1-{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-5-methylimidazolidin-2-ylidene)cyanamide. Rf=0.20 (25% EtOAc/hexanes). LCMS=643.3 (M+1)+. 1H NMR (C6D6, 500 MHz; atropisomers present, doubling of some peaks) δ 6.53-8.83 (m, 10H), 3.61-4.91 (m, 3H), 3.28-2.70 (m, 5H), 1.14-1.25 (m, 6H), −0.39-0.26 (m, 3H).

Workup

  1. temperaturecooled to room temperature
  2. filtrationfiltered
  3. customloaded directly onto a silica gel column for purification by flash chromatography with 10 to 40% EtOAc/hexanes

Sources & evidence

ORD record
ord-f8e3c5dcca13499099b0c9780201639f
Source dataset
uspto-grants-2014_05
Patent number
US08735435B2

Reaction notes

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