Trifluoroacetic acid → HCID 90067510, compound

HRID 929202Notes

Reaction equation

HRID 929202 reaction equation
C(O)(C(F)(F)F)=O.[CH3:8][O:9][C@@H:10]1[CH2:14][O:13][C@@H:12]2[C@H:15]([O:18][C:19]3[N:20](COCC[Si](C)(C)C)[C:21]4[C:22]([N:40]=3)=[N:23][C:24]([C:28]3[CH:33]=[CH:32][C:31]([C:34]5[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=5)=[CH:30][CH:29]=3)=[C:25]([Cl:27])[CH:26]=4)[CH2:16][O:17][C@H:11]12>C(Cl)Cl>[CH3:8][O:9][C@@H:10]1[CH2:14][O:13][C@@H:12]2[C@H:15]([O:18][C:19]3[NH:20][C:21]4[C:22]([N:40]=3)=[N:23][C:24]([C:28]3[CH:33]=[CH:32][C:31]([C:34]5[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=5)=[CH:30][CH:29]=3)=[C:25]([Cl:27])[CH:26]=4)[CH2:16][O:17][C@H:11]12

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 131735092HCID 131735092, compound

Product 1

HCID 90067510HCID 90067510, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (0.7 ml, 9.09 mmol) was added to a stirred solution of 2-[[2-[[(3R,3aR,6R,6aR)-3-methoxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-5-(4-phenylphenyl)-imidazo[4,5-b]pyridin-1-yl]methoxy]ethyl-trimethyl-silane in DCM (0.7 ml). The reaction mixture was stirred at room temperature. After 1.5 hours, the reaction mixture was evaporated under reduced pressure to give a colorless residue. This material was purified by preparative HPLC reverse phase (C-18), using a 30×150 mm Sunfire™ column and eluting with a 20%-100% acetonitrile/water+0.05% TFA gradient followed by a 100% acetonitrile+0.05% TFA flush. The product fractions were combined, evaporated under reduced pressure, and lyophilized from ethanol and benzene to give the title compound as a white solid. LC-MS: calculated for C25H22ClN3O4 463.13 observed m/e: 464.16 (M+H)+ (Rt 1.21/2 min); 1H NMR δ (ppm) (CD3OD): 8.10 (s, 1H), 7.78 (ab qt, J=8.2 Hz, J=11.5 Hz, 4H), 7.72 (d, J=8.0 Hz, 2H), 7.50 (t, J=7.8 Hz, 2H), 7.40 (t, J=7.5 Hz, 1H), 5.62 (qt, J=5.0 Hz, 1H), 5.02 (t, J=5.3 Hz, 1H), 4.65 (t, J=4.8 Hz, 1H), 4.18 (dd, J=4.4 Hz, J=10.6 Hz, 1H), 4.14 (dd, J=5.4 Hz, 10.6 Hz, 1H), 3.99-4.03 (m, 1H), 3.98 (t, J=7.2 Hz, 1H), 3.64 (t, J=8.3 Hz, 1H), 3.49 (s, 3H).

Workup

  1. customthe reaction mixture was evaporated under reduced pressure
  2. customto give a colorless residue
  3. customThis material was purified by preparative HPLC reverse phase (C-18)
  4. washeluting with a 20%-100% acetonitrile/water+0.05% TFA
  5. customflush
  6. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-45ccad1acf2a4a23baa5f5430f176f52
Source dataset
uspto-grants-2016_03
Patent number
US09290517B2

Reaction notes

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