Ammonia → HCID 89719285, compound

HRID 930196Notes

Reaction equation

HRID 930196 reaction equation
[N:1]1([CH2:7][CH2:8][CH2:9][NH:10][C:11]2[C:23]3[C:22]4[C:17](=[CH:18][C:19]([C:24]([O:26][CH3:27])=[O:25])=[CH:20][CH:21]=4)[NH:16][C:15]=3[N:14]=[C:13]([CH2:28][C:29]3[CH:34]=[CH:33][CH:32]=[C:31]([C:35](=[N:40]OS(C4C=CC(C)=CC=4)(=O)=O)[C:36]([F:39])([F:38])[F:37])[CH:30]=3)[N:12]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH3:52]>C(Cl)Cl>[N:1]1([CH2:7][CH2:8][CH2:9][NH:10][C:11]2[C:23]3[C:22]4[C:17](=[CH:18][C:19]([C:24]([O:26][CH3:27])=[O:25])=[CH:20][CH:21]=4)[NH:16][C:15]=3[N:14]=[C:13]([CH2:28][C:29]3[CH:34]=[CH:33][CH:32]=[C:31]([C:35]4([C:36]([F:39])([F:38])[F:37])[NH:52][NH:40]4)[CH:30]=3)[N:12]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

4

Reactant 2

HCID 222AmmoniaHCID 89717979HCID 89717979, compound

Product 1

HCID 89719285HCID 89719285, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
20 °C

Procedure

To a solution of methyl 4-((3-(piperidin-1-yl)propyl)amino)-2-(3-(2,2,2-trifluoro-1-((tosyloxy)imino)ethyl)benzyl)-9H-pyrimido[4,5-b]indole-7-carboxylate (0.188 g, 0.260 mmol) in DCM (5.00 mL) cooled to −78° C., ammonia (1.689 mL, 78 mmol) was added and the tube was sealed and warmed to 20° C. The reaction mixture turned blue over time and after 3.5 hours it was cooled again to −78° C. and then slowly warmed to 20° C. with septa+nitrogen outlet to evaporate most of the ammonia. After 3.5 hours, the reaction mixture was filtered over Buchner to remove most of the ammonium p-toluenesulfonate), the solids were washed with DCM (3×1.5 mL) and the filtrate was concentrated to dryness to give a yellow foam which was purified by flash chromatography to afford methyl 4-((3-(piperidin-1-yl)propyl)amino)-2-(3-(3-(trifluoromethyl)diaziridin-3-yl)benzyl)-9H-pyrimido[4,5-b]indole-7-carboxylate (115 mg, 78% yield) as a white foam: 1H NMR (400 MHz, DMSO-d6) δ ppm 1.31-1.43 (m, 2H) 1.50 (quin, J=5.3 Hz, 4H) 1.80 (dt, J=14.1, 7.0 Hz, 2H) 2.32 (m, J=6.7, 6.7 Hz, 6H) 3.58-3.67 (m, 2H) 3.88 (s, 3H) 3.93 (br. d, J=7.4 Hz, 1H) 4.05 (br. d, J=8.6 Hz, 1H) 4.07 (s, 2H) 7.32-7.43 (m, 3H) 7.47 (m, J=6.3 Hz, 1H) 7.59 (s, 1H) 7.81 (dd, J=8.4, 1.2 Hz, 1H) 7.99 (d, J=1.2 Hz, 1H) 8.35 (d, J=8.4 Hz, 1H) 12.07 (s, 1H); MS m/z 568.2 (M+H)+; HPLC >94%, RT=1.72 minutes.

Workup

  1. customthe tube was sealed
  2. temperatureit was cooled again to −78° C.
  3. temperatureslowly warmed to 20° C. with septa+nitrogen outlet
  4. customto evaporate most of the ammonia
  5. waitAfter 3.5 hours
  6. filtrationthe reaction mixture was filtered over Buchner
  7. customto remove most of the ammonium p-toluenesulfonate), the solids
  8. washwere washed with DCM (3×1.5 mL)
  9. concentrationthe filtrate was concentrated to dryness
  10. customto give a yellow foam which
  11. customwas purified by flash chromatography

Sources & evidence

ORD record
ord-cbcda508d9994b2293b774d120d2a59c
Source dataset
uspto-grants-2016_03
Patent number
US09296744B2

Reaction notes

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