Ammonia → HCID 89717640, compound

HRID 930209Notes

Reaction equation

HRID 930209 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][CH2:11][N:12]([CH3:58])[CH2:13][CH2:14][CH2:15][NH:16][C:17]1[C:29]2[C:28]3[C:23](=[CH:24][C:25]([C:30]([O:32][CH3:33])=[O:31])=[CH:26][CH:27]=3)[NH:22][C:21]=2[N:20]=[C:19]([CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[C:37]([C:41](=[N:46]OS(C3C=CC(C)=CC=3)(=O)=O)[C:42]([F:45])([F:44])[F:43])[CH:36]=2)[N:18]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH3:59]>C(Cl)Cl>[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][CH2:11][N:12]([CH3:58])[CH2:13][CH2:14][CH2:15][NH:16][C:17]1[C:29]2[C:28]3[C:23](=[CH:24][C:25]([C:30]([O:32][CH3:33])=[O:31])=[CH:26][CH:27]=3)[NH:22][C:21]=2[N:20]=[C:19]([CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[C:37]([C:41]3([C:42]([F:43])([F:44])[F:45])[NH:59][NH:46]3)[CH:36]=2)[N:18]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 222AmmoniaHCID 89719318HCID 89719318, compound

Product 1

HCID 89717640HCID 89717640, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
20 °C

Procedure

A solution of methyl 4-((3-((3-((tert-butoxycarbonyl)amino)propyl)(methyl)amino)propyl)amino)-2-(3-(2,2,2-trifluoro-1-((tosyloxy)imino)ethyl)benzyl)-9H-pyrimido[4,5-b]indole-7-carboxylate (0.217 g, 0.263 mmol) in DCM (5.07 mL) was cooled to −78° C. and ammonia (1.7 mL, 79 mmol) was condensed into the sealed tube. The mixture was allowed to slowly warm to 20° C. and stirred for 3 hours. After cooling again to −78° C., the sealed tube was fitted with a septa with gas outlet and slowly warmed to 20° C. to evaporate ammonia. After 3 hours, the mixture was concentrated to dryness and then purified by flash chromatography to afford methyl 4-((3-((3-((tert-butoxycarbonyl)amino)propyl)(methyl)amino)propyl)amino)-2-(3-(3-(trifluoromethyl)diaziridin-3-yl)benzyl)-9H-pyrimido[4,5-b]indole-7-carboxylate (139 mg, 79% yield) as a white foam: 1H NMR (400 MHz, DMSO-d6) δ ppm 1.34 (s, 9H) 1.52-1.62 (m, 2H) 1.72-1.89 (m, 2H) 2.08-2.25 (m, 3H) 2.30-2.44 (m, 4H) 2.94 (q, J=6.4 Hz, 2H) 3.64 (q, J=6.5 Hz, 2H) 3.88 (s, 3H) 3.93 (d, J=8.4 Hz, 1H) 4.04 (d, J=8.4 Hz, 1H) 4.08 (s, 2H) 6.78 (br. s., 1H) 7.31-7.41 (m, 2H) 7.44-7.50 (m, 1H) 7.54 (t, J=5.5 Hz, 1H) 7.59 (s, 1H) 7.83 (dd, J=8.4, 1.4 Hz, 1H) 7.99 (d, J=1.4 Hz, 1H) 8.27 (d, J=8.4 Hz, 1H) 12.07 (s, 1H); MS m/z 671.4 (M+H)+; HPLC 98.6% @ 220 nm and 96.4% @ 254 nm, RT=1.91 minutes.

Workup

  1. customcondensed into the sealed tube
  2. temperatureAfter cooling again to −78° C.
  3. customthe sealed tube was fitted with a septa with gas outlet
  4. temperatureslowly warmed to 20° C.
  5. customto evaporate ammonia
  6. waitAfter 3 hours
  7. concentrationthe mixture was concentrated to dryness
  8. custompurified by flash chromatography

Sources & evidence

ORD record
ord-78725893ce1f4daebd99d29084127c4e
Source dataset
uspto-grants-2016_03
Patent number
US09296744B2

Reaction notes

Loading…