Diisopropylethylamine → HCID 89404243, compound

HRID 1487013Notes

Reaction equation

HRID 1487013 reaction equation
[F:1][C:2]([F:24])([F:23])[C:3]1[CH:4]=[C:5]([C:13]2[N:17]=[CH:16][N:15](/[CH:18]=[CH:19]\[C:20](O)=[O:21])[N:14]=2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[C:25]([O:29][C:30](=[O:38])[NH:31][CH2:32][C:33]1([F:37])[CH2:36][NH:35][CH2:34]1)([CH3:28])([CH3:27])[CH3:26].C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.CCN(C(C)C)C(C)C>C(Cl)Cl>[C:25]([O:29][C:30](=[O:38])[NH:31][CH2:32][C:33]1([F:37])[CH2:34][N:35]([C:20](=[O:21])/[CH:19]=[CH:18]\[N:15]2[CH:16]=[N:17][C:13]([C:5]3[CH:6]=[C:7]([C:9]([F:10])([F:11])[F:12])[CH:8]=[C:3]([C:2]([F:23])([F:24])[F:1])[CH:4]=3)=[N:14]2)[CH2:36]1)([CH3:28])([CH3:26])[CH3:27]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 712507473-(Boc-aMino)-3-fluoroazetidineHCID 86703006(Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid

Product 1

HCID 89404243HCID 89404243, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-60 °C

Procedure

(Z)-3-(3-(3,5-Bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid (0.20 g, 0.56 mmol) was dissolved in DCM (10 mL). The reaction mixture was cooled to −60° C., at which temperature tert-butyl(3-fluoroazetidin-3-yl)methylcarbamate (0.127 g, 0.62 mmol), was added, followed by T3P (50% in EtOAc) (0.434 g, 0.67 mmol). DIPEA (0.144 g, 1.11 mmol) was then introduced slowly. The clear reaction mixture was stirred at −60° C. for a further 45 min. The reaction mixture was concentrated under reduced pressure to obtain crude product, which was purified by column chromatography (0-15% ethyl actetate-hexane) to afford 150 mg of (Z)-tert-butyl(1-(3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acryloyl)-3-fluoroazetidin-3-yl)methylcarbamate (Yield 50%). 1H NMR (400 MHz, CDCl3, ppm) δ=9.7 (s, 1H); 8.63 (s, 2H); 7.94 (s, 1H); 7.24-7.21 (d, J=10.8 Hz, 1H); 5.67-5.64 (d, J=10.8, 1H); 4.41-4.16 (m, 4H); 3.76-3.54 (m, 3H).

Workup

  1. additionwas added
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. customto obtain crude product, which
  4. customwas purified by column chromatography (0-15% ethyl actetate-hexane)

Sources & evidence

ORD record
ord-f3b94e3d382c461e9fd475286828f804
Source dataset
uspto-grants-2016_08
Patent number
US09428490B2

Reaction notes

Loading…