3,3-Dimethyl-1-(trifluoromethyl)-1,2-benziodoxole → HCID 86711406, compound

HRID 926336Notes

Reaction equation

HRID 926336 reaction equation
[CH:1]1([C:4]2[CH:13]=[CH:12][CH:11]=[C:10]3[C:5]=2[CH2:6][CH2:7][N:8]2[C:18](=[O:19])[CH2:17][N:16]=[C:15]([N:20]4[CH:24]=[C:23]([CH2:25][OH:26])[N:22]=[CH:21]4)[CH:14]=[C:9]23)[CH2:3][CH2:2]1.CC1(C)C2C=CC=CC=2I([C:37]([F:40])([F:39])[F:38])O1>C(Cl)(Cl)Cl.[Zn](N(S(C(F)(F)F)(=O)=O)S(C(F)(F)F)(=O)=O)N(S(C(F)(F)F)(=O)=O)S(C(F)(F)F)(=O)=O>[CH:1]1([C:4]2[CH:13]=[CH:12][CH:11]=[C:10]3[C:5]=2[CH2:6][CH2:7][N:8]2[C:18](=[O:19])[CH2:17][N:16]=[C:15]([N:20]4[CH:24]=[C:23]([CH2:25][O:26][C:37]([F:40])([F:39])[F:38])[N:22]=[CH:21]4)[CH:14]=[C:9]23)[CH2:3][CH2:2]1

Participants

5

Reactant 2

HCID 160435723,3-Dimethyl-1-(trifluoromethyl)-1,2-benziodoxole2×HCID 86711407HCID 86711407, compound

Product 1

HCID 86711406HCID 86711406, compoundYield 1.9%

Reagents, catalysts & solvents 2

HCID 178527593HCID 178527593, compoundCatalyst2×HCID 6212ChloroformSolvent

Procedure

A solution of 9-cyclopropyl-2-(4-(hydroxymethyl)-1H-imidazol-1-yl)-7,8-dihydro-[1,4]diazepino[7,1-a]isoquinolin-5(4H)-one (135 mg, 0.38 mmol) in CHCl3 (50 mL) under Ar, was treated with 3,3-Dimethyl-1-(trifluoromethyl)-1,2-benziodoxole (245 mg, 0.78 mmol) and Zn(NTf2)2 (242 mg, 0.39 mmol). The mixture was stirred at RT for 16 h, and then treated again with 3,3-Dimethyl-1-(trifluoromethyl)-1,2-benziodoxole (245 mg, 0.78 mmol) and Zn(NTf2)2 (242 mg, 0.39 mmol). After 24 h, the mixture was poured onto H2O and extracted with DCM. The combined org. layers were then dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by flash chromatography (SiO2, DCM/MeOH 100:0 to 95:5) and by SFC (column: PPU 5 m, 250×30 mm, 60 A, Princeton; eluent: isocratic 20% MeOH/CO2 for 11 min; flow 100 mL/min; UV detection at 220 nm) to give the title compound (3 mg). UPLC-MS: MS 417.2 (M+H+); UPLC rt 1.15 min. 1H NMR (400 MHz, DMSO-d6): δ ppm 0.56-0.71 (m, 2H); 0.93-1.05 (m, 2H); 1.91-2.04 (m, 1H); 3.14-3.20 (m, 2H); 3.89-4.01 (m, 2H); 4.34 (br s, 2H); 5.00 (s, 2H); 7.03 (s, 1H); 7.18-7.26 (m, 1H); 7.26-7.34 (m, 1H); 7.69-7.85 (m, 2H); 8.25 (s, 1H).

Workup

  1. waitAfter 24 h
  2. additionthe mixture was poured onto H2O
  3. extractionextracted with DCM
  4. dry with materiallayers were then dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by flash chromatography (SiO2, DCM/MeOH 100:0 to 95:5) and by SFC (column: PPU 5 m, 250×30 mm, 60 A, Princeton; eluent: isocratic 20% MeOH/CO2 for 11 min; flow 100 mL/min; UV detection at 220 nm)

Sources & evidence

ORD record
ord-3b6248ef0cd147879046a1f5241e9de8
Source dataset
uspto-grants-2016_03
Patent number
US09284331B2

Reaction notes

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