Trifluoroacetic acid → HCID 178519174, compound

HRID 634450Notes

Reaction equation

HRID 634450 reaction equation
C([N:20]1[CH:28]=[N:27][C:26]2[C:21]1=[N:22][CH:23]=[N:24][C:25]=2[NH:29]C(=O)OC(C)(C)C)(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[H-].[Na+].Br[CH2:40][C:41]1[O:42][C:43](=[O:58])[C:44]2[C:49]([C:50]=1[C:51]1[CH:56]=[CH:55][CH:54]=[C:53]([F:57])[CH:52]=1)=[CH:48][CH:47]=[CH:46][CH:45]=2.C(O)(C(F)(F)F)=O>CN(C=O)C.CCOC(C)=O.C(Cl)Cl>[N:24]1[C:25]([NH:29][CH2:40][C:41]2[O:42][C:43](=[O:58])[C:44]3[C:49]([C:50]=2[C:51]2[CH:56]=[CH:55][CH:54]=[C:53]([F:57])[CH:52]=2)=[CH:48][CH:47]=[CH:46][CH:45]=3)=[C:26]2[C:21]([NH:20][CH:28]=[N:27]2)=[N:22][CH:23]=1

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 24758Sodium hydrideHCID 70974658tert-butyl N-(9-tritylpurin-6-yl)carbamateHCID 1181312373-(Bromomethyl)-4-(3-fluorophenyl)-1H-isochromen-1-one2×

Product 1

HCID 178519174HCID 178519174, compoundYield 34.4%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Tert-butyl 9-trityl-9H-purin-6-ylcarbamate (93 mg, 0.195 mmol) and 50% dispersion in mineral oil NaH (9.4 mg, 0.195 mmol) were dissolved in DMF (0.2 ml) at 0° C. A solution of 3-(bromomethyl)-4-(3-fluorophenyl)-1H-isochromen-1-one (intermediate C4, 50 mg, 0.150 mmol) in DMF (0.6 mL) was then added. The reaction mixture was stirred at 0° C. for 5 min and at RT for 15 min. The reaction mixture was then diluted with EtOAc (20 mL) and washed with 0.2 M HClaqueous, sat NaClaqueous dried over Na2SO4 and concentrated under reduced pressure to give the crude yellow oil. The crude was reacted with TFA (1.5 ml) in DCM (2 ml) for 1 hrs. Then it was diluted with DCM and dried under reduced pressure to give an yellow oil. This was purified via reverse phase chromatography with a Biotage C18 30 g SNAP column (Phase A, water 95%, ACN 5%, formic acid 0.1%); Phase B ACN 95%, water 5%, formic acid 0.1%) to give the title compound (20 mg, 34.4%) as colourless solid.

Workup

  1. washwashed with 0.2 M HClaqueous
  2. dry with materialsat NaClaqueous dried over Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. customto give the crude yellow oil
  5. customdried under reduced pressure
  6. customto give an yellow oil
  7. customThis was purified via reverse phase chromatography with a Biotage C18 30 g SNAP column (Phase A, water 95%, ACN 5%, formic acid 0.1%)

Sources & evidence

ORD record
ord-8a586fd974c24d6cacf15185785b64e5
Source dataset
uspto-grants-2016_04
Patent number
US09321776B2

Reaction notes

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