Acetamidine monohydrochloride → 8-Chloro-2-[5-methyl-2-(2,2,2-trifluoro-ethyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1,3a,9-triaza-benzo[e]azulene

HRID 1530643ノート

反応式

HRID 1530643 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][N:15]=1)[C:12]1[N:8]([CH:9]=[C:10](I)[N:11]=1)[CH2:7][CH2:6][O:5]2.Cl.[C:18]([NH2:21])(=[NH:20])[CH3:19].[C:22]1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.Cl.[F:65][C:66]([F:71])([F:70])[CH2:67][NH:68]N>CN(C=O)C.C(O)(=O)C.CC([O-])=O.CC([O-])=O.[Pd+2].CCN(CC)CC>[Cl:1][C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][N:15]=1)[C:12]1[N:8]([CH:9]=[C:10]([C:22]3[N:68]([CH2:67][C:66]([F:71])([F:70])[F:65])[N:21]=[C:18]([CH3:19])[N:20]=3)[N:11]=1)[CH2:7][CH2:6][O:5]2

参加物

9

反応物 4

HCID 67170Acetamidine monohydrochlorideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 21934076(2,2,2-Trifluoroethyl)hydrazine hydrochlorideHCID 582047809-Chloro-2-iodo-5,6-dihydroimidazo[1,2-d]pyrido[3,4-f][1,4]oxazepine

生成物 1

HCID 866523128-Chloro-2-[5-methyl-2-(2,2,2-trifluoro-ethyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1,3a,9-triaza-benzo[e]azulene収率 76%

試薬・触媒・溶媒 4

HCID 167845palladium(II) acetate触媒HCID 176Acetic Acid溶媒HCID 6228Dimethylformamide溶媒HCID 8471Triethylamine溶媒

反応条件

温度
40 °C

実験手順

A mixture of 12-chloro-4-iodo-9-oxa-3,6,13-triazatricyclo[8.4.0.02,6]tetradeca1 (14),2,4,10,12-pentaene (1.60 g, 4.60 mmol) and acetamidine hydrochloride (481 g, 5.06 mmol), Et3N (4.00 mL), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos, 532 mg, 0.920 mmol), and Pd(OAc)2 (103 mg, 0.460 mmol) in DMF (20.0 mL) was heated under carbon monoxide atmosphere at 40° C. for 3 h. After cooling to room temperature, a solution of (2,2,2-trifluoroethyl)hydrazine hydrochloride (800 mg, 5.32 mmol) in acetic acid (15.0 mL) was added. The resultant mixture was further heated at 65° C. for 3 h. After concentratin, the residue was extracted with ethyl acetate, washed with brine, dried over MgSO4, filtered, and evaporated. The crude product was purified by reverse phase Combiflash eluting with a 0-40% gradient of CH3CN in 0.5% NH4HCO3 to give 12-chloro-4-[3-methyl-1-(2,2,2-trifluoroethyl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6,13-triazatricyclo[8.4.0.02,6]tetradeca1(14),2,4,10,12-pentaene (1.35 mg, 76% yield) as pale yellow solid. LCMS (ESI) m/z: 385.1 [M+H+].

後処理

  1. temperatureAfter cooling to room temperature
  2. extractionthe residue was extracted with ethyl acetate
  3. washwashed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude product was purified by reverse phase Combiflash
  8. washeluting with a 0-40% gradient of CH3CN in 0.5% NH4HCO3

出典と根拠

ORDレコード
ord-8426f00e3ba3486ba40bcda2936cdaac
出典データセット
uspto-grants-2015_07
特許番号
US09090628B2

反応ノート

読み込み中…