Trifluoroacetic acid → N-(2-Diethylamino-ethyl)-4-(3-indan-5-yl-3H-[1,2,3]triazolo[4,5-d]-pyrimidin-5-ylamino)-benzamide

HRID 229325

Reaction equation

HRID 229325 reaction equation
Cl[C:2]1[N:7]=[C:6](Cl)[C:5]([N+:9]([O-])=O)=[CH:4][N:3]=1.[NH2:12][C:13]1[CH:14]=[C:15]([CH:20]=[CH:21][CH:22]=1)[C:16](NC)=O.Cl.[NH2:24][C:25]1[CH:40]=[CH:39][C:28]([C:29]([NH:31][CH2:32][CH2:33][N:34]([CH2:37][CH3:38])[CH2:35][CH3:36])=[O:30])=[CH:27][CH:26]=1.[N:41]([O-])=O.[Na+].[C:45](O)([C:47](F)(F)F)=O>C1COCC1.C(O)(C)C.O.[Zn].CC(O)=O.CN(C)C=O>[CH2:35]([N:34]([CH2:37][CH3:38])[CH2:33][CH2:32][NH:31][C:29](=[O:30])[C:28]1[CH:39]=[CH:40][C:25]([NH:24][C:2]2[N:3]=[CH:4][C:5]3[N:9]=[N:41][N:12]([C:13]4[CH:14]=[C:15]5[C:20](=[CH:21][CH:22]=4)[CH2:47][CH2:45][CH2:16]5)[C:6]=3[N:7]=2)=[CH:26][CH:27]=1)[CH3:36]

Participants

12

Reactant 5

HCID 6422Trifluoroacetic acidHCID 66068Procainamide HydrochlorideHCID 5212662,4-Dichloro-5-nitropyrimidineHCID 6765263-Amino-N-methylbenzamideHCID 23668193Sodium Nitrite

Product 1

HCID 11712520N-(2-Diethylamino-ethyl)-4-(3-indan-5-yl-3H-[1,2,3]triazolo[4,5-d]-pyrimidin-5-ylamino)-benzamide

Reagents, catalysts & solvents 6

HCID 23994ZincCatalystHCID 176Acetic AcidSolvent2×HCID 962WaterSolvent2×HCID 3776IsopropanolSolvent2×HCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 2,4-dichloro-5-nitropyrimidine (25.0 mg, 0.13 mmol) in THF (0.2 mL) was added a solution of 3-amino-N-methyl-benzamide (19.5 mg, 0.13 mmol) in isopropyl alcohol (0.5 mL)/dimethylformamide (0.3 mL), and CsHCO3 (25.2 mg, 0.13 mmol) in water (0.016 mL total volume). The mixture was stirred at rt for 1.5 hr at which time 4-amino-N-(2-diethylamino-ethyl)-benzamide HCl (procainamide: hydrochloride) (38.9 mg, 0.14 mmol) in isopropyl alcohol (0.5 mL)/dimethylformamide (0.3 mL) was added. The mixture was stirred at 50° C. for 20 hr. cooled to rt, and acetic acid (0.1 mL) was added. To the resulting slurry was added Zn dust (45 mg, 0.69 mmol); after stirring for 15 min at rt, the reaction solution was loaded onto a 1 g silica gel SPE cartridge and eluted with 6 mL of MeOH. The eluent was concentrated at reduced pressure, dried at approximately 1 mm Hg for 18 hr. and re-suspended in MeOH (1.0 mL). To this slurry was added HOAc (0.05 mL) and sodium nitrite (0.09 g, 1.3 mmol) in water (total volume 0.2 mL). The mixture was stirred at rt for 11 hr. loaded onto a 1 g C-18 SPE cartridge, and eluted with 6 mL of MeOH. The eluent was concentrated and the resulting residue was purified by reverse-phase liquid chromatography using a gradient of 90:10 (water:acetonitrile, with 0.1% TFA) to 10:90 (water:acetonitrile, with 0.1% TFA) to furnish (7) (0.0128 g, 0.018 mmol) as the bis TFA salt. HRMS (ES-TOF) calcd. for C25H30N9O2 m/z 488.2522 (M+H),+ found: 488.2514.

Workup

  1. additionwas added
  2. temperaturecooled to rt
  3. stirringafter stirring for 15 min at rt
  4. washeluted with 6 mL of MeOH
  5. concentrationThe eluent was concentrated at reduced pressure
  6. customdried at approximately 1 mm Hg for 18 hr
  7. stirringThe mixture was stirred at rt for 11 hr
  8. washeluted with 6 mL of MeOH
  9. concentrationThe eluent was concentrated
  10. customthe resulting residue was purified by reverse-phase liquid chromatography

Sources & evidence

ORD record
ord-d5421c61c7e141358c5d7b765c6041f5
Source dataset
uspto-grants-2009_07
Patent number
US07563781B2

Linked notes

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