Hydroxyamine hydrochloride → HCID 89717373, compound

HRID 930194Notes

Reaction equation

HRID 930194 reaction equation
Cl.[NH2:2][OH:3].[N:4]1([CH2:10][CH2:11][CH2:12][NH:13][C:14]2[C:26]3[C:25]4[C:20](=[CH:21][C:22]([C:27]([O:29][CH3:30])=[O:28])=[CH:23][CH:24]=4)[NH:19][C:18]=3[N:17]=[C:16]([CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[C:34]([C:38](=O)[C:39]([F:42])([F:41])[F:40])[CH:33]=3)[N:15]=2)[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5]1>CO.N1C=CC=CC=1>[N:4]1([CH2:10][CH2:11][CH2:12][NH:13][C:14]2[C:26]3[C:25]4[C:20](=[CH:21][C:22]([C:27]([O:29][CH3:30])=[O:28])=[CH:23][CH:24]=4)[NH:19][C:18]=3[N:17]=[C:16]([CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[C:34]([C:38](=[N:2][OH:3])[C:39]([F:40])([F:41])[F:42])[CH:33]=3)[N:15]=2)[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9]1

Participants

5

Reactant 2

HCID 443297Hydroxyamine hydrochlorideHCID 71714973HCID 71714973, compound

Product 1

HCID 89717373HCID 89717373, compoundYield 100.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1049PyridineSolvent

Conditions

Temperature
60 °C

Procedure

Hydroxylamine hydrochloride (0.08 g, 1.2 mmol) was added to methyl 4-((3-(piperidin-1-yl)propyl)amino)-2-(3-(2,2,2-trifluoroacetyl)benzyl)-9H-pyrimido[4,5-b]indole-7-carboxylate (compound of Example 33) (0.285 g, 0.515 mmol) in MeOH (4.00 mL) and pyridine (0.666 mL) to give a yellow solution. After heating at 60° C. 5 days, the mixture was concentrated to dryness and the residue was dissolved into DCM (75 mL) and MeOH (15 mL) and this solution was washed with sat. NaHCO3 (20 mL). The aqueous layer was extracted two time with a mixture of CH2Cl2 (50 mL) and MeOH (10 mL) and the combined organic layers were dried over anh. MgSO4, filtered and concentrated to dryness to give methyl 4-((3-(piperidin-1-yl)propyl)amino)-2-(3-(2,2,2-trifluoro-1-(hydroxyimino)ethyl)benzyl)-9H-pyrimido[4,5-b]indole-7-carboxylate (293 mg, 100% yield) as an off-white solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 1.32-1.43 (m, 2H) 1.44-1.56 (m, 4H) 1.76-1.87 (m, 2H) 2.23-2.44 (m, 6H) 3.57-3.67 (m, 2H) 3.88 (s, 3H) 4.04-4.12 (m, 2H) 7.25-7.33 (m, 1H) 7.34-7.46 (m, 2H) 7.50 (m, J=7.6, 4.1 Hz, 1H) 7.55 (d, J=7.4 Hz, 1H) 7.81 (dd, J=8.2, 1.2 Hz, 1H) 7.99 (d, J=1.2 Hz, 1H) 8.36 (d, J=8.2 Hz, 1H) 12.07 (d, J=3.5 Hz, 1H); MS m/z 569.2 (M+H)+; HPLC >95%, RT=1.88 minutes.

Workup

  1. customto give a yellow solution
  2. concentration5 days, the mixture was concentrated to dryness
  3. dissolutionthe residue was dissolved into DCM (75 mL) and MeOH (15 mL)
  4. washthis solution was washed with sat. NaHCO3 (20 mL)
  5. extractionThe aqueous layer was extracted two time
  6. additionwith a mixture of CH2Cl2 (50 mL) and MeOH (10 mL)
  7. dry with materialthe combined organic layers were dried over anh. MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-0911259843674a138de6d8a7d63a6ba5
Source dataset
uspto-grants-2016_03
Patent number
US09296744B2

Reaction notes

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