1,1,1-Trifluoro-2-iodoethane → HCID 118413229, compound

HRID 929199Notes

Reaction equation

HRID 929199 reaction equation
I[CH2:2][C:3]([F:6])([F:5])[F:4].[CH2:7]([N:10]1[C:18]2[C:13](=[N:14][C:15]([C:20]3[CH:25]=[CH:24][C:23]([N:26]4[CH:30]=[C:29]5[CH2:31][NH:32][CH2:33][C:28]5=[N:27]4)=[CH:22][CH:21]=3)=[C:16]([Cl:19])[CH:17]=2)[N:12]=[C:11]1[O:34][C@H:35]1[C@H:39]2[O:40][CH2:41][C@@H:42]([OH:43])[C@H:38]2[O:37][CH2:36]1)[CH:8]=[CH2:9].C(N(CC)C(C)C)(C)C.FC(F)(F)S(OCC(F)(F)F)(=O)=O>O1CCOCC1>[CH2:7]([N:10]1[C:18]2[C:13](=[N:14][C:15]([C:20]3[CH:21]=[CH:22][C:23]([N:26]4[CH:30]=[C:29]5[CH2:31][N:32]([CH2:2][C:3]([F:6])([F:5])[F:4])[CH2:33][C:28]5=[N:27]4)=[CH:24][CH:25]=3)=[C:16]([Cl:19])[CH:17]=2)[N:12]=[C:11]1[O:34][C@H:35]1[C@H:39]2[O:40][CH2:41][C@@H:42]([OH:43])[C@H:38]2[O:37][CH2:36]1)[CH:8]=[CH2:9]

Participants

6

Reactant 4

HCID 677091,1,1-Trifluoro-2-iodoethaneHCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 81531DiisopropylethylamineHCID 90067288HCID 90067288, compound

Product 1

HCID 118413229HCID 118413229, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
80 °C

Procedure

2-iodo-1,1,1-trifluoroethane (12.5 μl, 0.127 mmol) was added to a stirred solution of (3R,3aR,6R,6aR)-6-[1-allyl-6-chloro-5-[4-(5,6-dihydro-4H-pyrrolo[3,4-c]pyrazol-2-yl)phenyl]imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol (59.9 mg, 0.115 mmol) in dioxane (0.46 ml). The reaction mixture was a pale yellow solution that was heated to 80° C. After 2 days, N,N-diisopropylethylamine (40 μl, 0.229 mmol), 2,2,2-trifluoroethyl trifluoromethane-sulfonate (34 μl, 0.236 mmol), and additional dioxane (0.2 ml) were added to the reaction mixture. After stirring an additional 18 hours, the reaction mixture was cooled to room temperature. The reaction mixture was evaporated under reduced pressure to give a dark amber residue. The residue was purified by preparative HPLC reverse phase (C-18), using a 30×150 mm Sunfire™ column and eluting with a 20%-80% acetonitrile/water+0.05% TFA gradient followed by a 80% acetonitrile/water+0.05% TFA flush. The product fractions were combined and evaporated under reduced pressure to give the desired product as an amber residue. LC-MS: calculated for C28H26ClF3N6O4 602.17 observed m/e: 603.19 (M+H)+ (Rt 1.20/2 min)

Workup

  1. temperaturethe reaction mixture was cooled to room temperature
  2. customThe reaction mixture was evaporated under reduced pressure
  3. customto give a dark amber residue
  4. customThe residue was purified by preparative HPLC reverse phase (C-18)
  5. washeluting with a 20%-80% acetonitrile/water+0.05% TFA
  6. customflush
  7. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-97a693be9e5445859c213e6403b04ef8
Source dataset
uspto-grants-2016_03
Patent number
US09290517B2

Reaction notes

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