Trifluoromethanesulfonic acid → 7-(2-Aminopyrimidin-5-yl)-1-{[(1r)-1-cyclopropyl-2,2,2-trifluoroethyl]amino}-8-iodo-5h-pyrido[4,3-b]indole-4-carboxamide

HRID 1971026Notes

Reaction equation

HRID 1971026 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]3[C:12]4[C:20]([NH:21][C@H:22]([CH:27]5[CH2:29][CH2:28]5)[C:23]([F:26])([F:25])[F:24])=[N:19][CH:18]=[C:17]([C:30]([NH2:32])=[O:31])[C:13]=4[NH:14][C:15]=3[CH:16]=2)=[CH:4][N:3]=1.[B-](F)(F)(F)F.C1C=CN=CC=1.C1C=CN=CC=1.[IH2+:50].FC(F)(F)S(O)(=O)=O.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:8]2[C:9]([I:50])=[CH:10][C:11]3[C:12]4[C:20]([NH:21][C@H:22]([CH:27]5[CH2:29][CH2:28]5)[C:23]([F:25])([F:24])[F:26])=[N:19][CH:18]=[C:17]([C:30]([NH2:32])=[O:31])[C:13]=4[NH:14][C:15]=3[CH:16]=2)=[CH:6][N:7]=1

Participants

6

Reactant 4

HCID 62406Trifluoromethanesulfonic acid2×HCID 516892Sodium BicarbonateHCID 10883201Bis(pyridine)iodonium tetrafluoroborate2×HCID 426229347-(2-Aminopyrimidin-5-yl)-1-{[(1r)-1-cyclopropyl-2,2,2-trifluoroethyl]amino}-5h-pyrido[4,3-b]indole-4-carboxamide

Product 1

HCID 426360827-(2-Aminopyrimidin-5-yl)-1-{[(1r)-1-cyclopropyl-2,2,2-trifluoroethyl]amino}-8-iodo-5h-pyrido[4,3-b]indole-4-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred slurry of 7-(2-aminopyrimidin-5-yl)-1-{[(1R)-1-cyclopropyl-2,2,2-trifluoroethyl]amino}-5H-pyrido[4,3-b]indole-4-carboxamide (60 mg, 0.14 mmol) and bis(pyridine)iodonium tetrafluoroborate (152 mg, 0.41 mmol) in DCM (2.5 mL) was added trifluoromethanesulfonic acid (0.11 mL, 1.2 mmol). The reaction mixture was left to stir for 2 d, treated with additional bis(pyridine)iodonium tetrafluoroborate (152 mg, 0.41 mmol) and trifluoromethanesulfonic acid (0.07 mL, 0.8 mmol), and left to stir for 6 h. The mixture was diluted with DCM and treated with sodium bicarbonate solution. The mixture was extracted with EtOAc, and the combined organics were washed with brine, dried (sodium sulfate), concentrated, and purified by flash chromatography to afford the title compound. 1H NMR (600 MHz, CD3SOCD3) δ 11.78 (s, 1H); 9.02 (s, 1H), 8.51 (s, 1H); 8.23 (s, 2H); 7.92 (br s, 1H); 7.70 (s, 1H); 7.78 (br s, 1H); 7.77 (d, 1H); 6.80 (s, 2H); 4.87 (m, 1H); 1.58 (m, 1H); 0.73 (m, 1H); 0.62 (m, 1H); 0.54 (m, 1H); 0.32 (m, 1H). LRMS (APCI) calc'd for (C21H17IF3N7O) [M+H]+, 568.0. found 568.0.

Workup

  1. waitThe reaction mixture was left
  2. waitleft
  3. stirringto stir for 6 h
  4. extractionThe mixture was extracted with EtOAc
  5. washthe combined organics were washed with brine
  6. dry with materialdried (sodium sulfate)
  7. concentrationconcentrated
  8. custompurified by flash chromatography

Sources & evidence

ORD record
ord-8aac347ff4004cb6885173fd9474f421
Source dataset
uspto-grants-2013_04
Patent number
US08431569B2

Reaction notes

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