Trifluoroacetic acid → HCID 118413232, compound

HRID 929219Notes

Reaction equation

HRID 929219 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]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]([OH:47])[C@H:42]4[O:41][CH2:40]3)=[N:27][C:5]2=[N:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([N:14]2[CH2:17][C:16]3([CH2:20][N:19]([C:21]4[N:26]=[CH:25][CH:24]=[CH:23][N:22]=4)[CH2:18]3)[CH2:15]2)=[CH:10][CH:9]=1.[C:48]([OH:54])([C:50]([F:53])([F:52])[F:51])=[O:49]>C(Cl)Cl.CO>[F:51][C:50]([F:53])([F:52])[C:48]([OH:54])=[O:49].[Cl:1][C:2]1[CH:3]=[C:4]2[NH:29][C:28]([O:38][C@H:39]3[C@H:43]4[O:44][CH2:45][C@@H:46]([OH:47])[C@H:42]4[O:41][CH2:40]3)=[N:27][C:5]2=[N:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([N:14]2[CH2:17][C:16]3([CH2:18][N:19]([C:21]4[N:26]=[CH:25][CH:24]=[CH:23][N:22]=4)[CH2:20]3)[CH2:15]2)=[CH:10][CH:9]=1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 131735096HCID 131735096, compound

Product 1

HCID 118413232HCID 118413232, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-(6-pyrimidin-2-yl-2,6-diazaspiro[3,3]heptan-2-yl)phenyl]-1-(2-trimethylsilylethoxy-methyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol (54.3 mg, 0.08 mmol) in TFA (0.5 mL) and DCM (0.5 mL) was stirred at room temperature. After 2 hours, the reaction mixture was evaporated to give an oil. The oil was dissolved in MeOH (1 mL) and 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/water+0.05% TFA flush. The desired fractions were combined, evaporated under reduced pressure, and lyophilized from ethanol and benzene to give the title compound as a solid. LC-MS: calculated for C27H26ClN7O4 547.17 observed m/e: 548.35 (M+H)+ (Rt 0.70/2 min); 1H NMR δ (ppm) (CD3OD): 8.44 (d, 2H), 7.96 (s, 1H), 7.56 (d, 2H), 6.81 (m, 1H), 6.65 (d, 2H), 5.58 (qt, 1H), 4.96 (t, 1H), 4.48 (t, 1H), 4.43 (s, 4H), 4.26-4.31 (m, 1H), 4.18 (s, 4H), 4.16 (dd, 1H), 4.12 (dd, 1H), 3.90 (t, 1H), 3.60 (t, 1H).

Workup

  1. customthe reaction mixture was evaporated
  2. customto give an oil
  3. custompurified 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-3b24975f0efc449aa5c87f4e58151f07
Source dataset
uspto-grants-2016_03
Patent number
US09290517B2

Reaction notes

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