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

反応式

HRID 229325 の反応式
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]

参加物

12

反応物 5

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

生成物 1

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

試薬・触媒・溶媒 6

HCID 23994Zinc触媒HCID 176Acetic Acid溶媒2 回HCID 962Water溶媒2 回HCID 3776Isopropanol溶媒2 回HCID 6228Dimethylformamide溶媒2 回HCID 8028Tetrahydrofuran溶媒

反応条件

温度
50 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-d5421c61c7e141358c5d7b765c6041f5
出典データセット
uspto-grants-2009_07
特許番号
US07563781B2

関連ノート

読み込み中…