Trifluoroacetic acid → HCID 90067328, compound

HRID 929203Notes

Reaction equation

HRID 929203 reaction equation
C(O)(C(F)(F)F)=O.[Cl:8][C:9]1[CH:10]=[C:11]2[N:29](COCC[Si](C)(C)C)[C:28]([O:38][C@H:39]3[C@H:43]4[O:44][CH2:45][C@@H:46]([O:47][CH2:48][CH:49]([OH:52])[CH2:50][OH:51])[C@H:42]4[O:41][CH2:40]3)=[N:27][C:12]2=[N:13][C:14]=1[C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:17][CH:16]=1.C[Si](C)(C)[O-].[K+]>C(Cl)Cl.C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]2[NH:29][C:28]([O:38][C@H:39]3[C@H:43]4[O:44][CH2:45][C@@H:46]([O:47][CH2:48][CH:49]([OH:52])[CH2:50][OH:51])[C@H:42]4[O:41][CH2:40]3)=[N:27][C:12]2=[N:13][C:14]=1[C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:17][CH:16]=1

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 23668039Potassium trimethylsilanolate2×HCID 131735093HCID 131735093, compound

Product 1

HCID 90067328HCID 90067328, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

TFA (0.25 ml, 3.24 mmol) was added to a stirred solution of 3-[[(3R,3aR,6R,6aR)-6-[6-chloro-5-(4-phenylphenyl)-1-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-yl]oxy]propane-1,2-diol (6.1 mg, 9.32 μmol) in DCM (0.25 ml). The reaction mixture was stirred at room temperature. After 2.5 hours, the reaction mixture was evaporated under reduced pressure. Potassium trimethylsilanolate (9.2 mg, 0.072 mmol) was added to a stirred solution of the residue in THF (0.5 ml). The reaction mixture was stirred at room temperature. After 1.5 hours, additional potassium trimethylsilanolate (18.2 mg, 0.142 mmol) was added to the reaction mixture. After an additional 1.5 hours, the reaction mixture was evaporated under reduced pressure to give a pale amber 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 C27H26ClN3O6 523.15 observed m/e: 524.22 (M+H)+ (Rt 1.16/2 min); 1H NMR δ (ppm) (CD3OD): 7.98 (s, 1H), 7.74-7.78 (m, 4H), 7.71 (d, J=7.4 Hz, 2H), 7.48 (t, J=7.7 Hz, 2H), 7.39 (t, J=7.4 Hz, 1H), 5.59 (qt, J=5.1 Hz, 1H), 5.01 (t, J=5.3 Hz, 1H), 4.65 (t, J=5.0 Hz, 1H), 4.13-4.17 (m, 3H), 3.98-4.01 (m, 1H), 3.54-3.81 (m, 6H).

Workup

  1. customthe reaction mixture was evaporated under reduced pressure
  2. stirringThe reaction mixture was stirred at room temperature
  3. waitAfter 1.5 hours
  4. waitAfter an additional 1.5 hours
  5. customthe reaction mixture was evaporated under reduced pressure
  6. customto give a pale amber residue
  7. customThis material was purified by preparative HPLC reverse phase (C-18)
  8. washeluting with a 20%-100% acetonitrile/water+0.05% TFA
  9. customflush
  10. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-585f8a5e6f904653850d0d00b15552ab
Source dataset
uspto-grants-2016_03
Patent number
US09290517B2

Reaction notes

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