Acetamidine → 12-chloro-4-[3-methyl-1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6,13-triazatricyclo[8.4.0.02,6]tetra-deca1(14),2,4,10,12-pentaene

HRID 1530638ノート

反応式

HRID 1530638 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.[C:17](=[NH:20])([NH2:19])[CH3:18].[CH3:21][C:22]1([CH3:62])C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.COC(C)[CH2:66][NH:67]N>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2].C(O)(=O)C>[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:66]3[N:67]([CH:22]([CH3:62])[CH3:21])[N:19]=[C:17]([CH3:18])[N:20]=3)[N:11]=1)[CH2:7][CH2:6][O:5]2

参加物

8

反応物 4

HCID 67171AcetamidineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 582047809-Chloro-2-iodo-5,6-dihydroimidazo[1,2-d]pyrido[3,4-f][1,4]oxazepineHCID 86671471(2-Methoxypropyl)hydrazine

生成物 1

HCID 8893255312-chloro-4-[3-methyl-1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6,13-triazatricyclo[8.4.0.02,6]tetra-deca1(14),2,4,10,12-pentaene収率 338.4%

試薬・触媒・溶媒 3

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

反応条件

温度
40 °C

実験手順

To a solution of 12-chloro-4-iodo-9-oxa-3,6,13-triazatricyclo[8.4.0.02,6]tetradeca-1(14),2,4,10,12-pentaene (2.0 g, 5.8 mmol) in dry DMF (20 mL) was added hydrochloric acetimidamide (595 mg, 6.30 mmol), Pd(OAc)2 (130 mg, 0.580 mmol), and Xantphos (695 mg, 1.2 mmol). The mixture was stirred at 40° C. for 3 h under carbon monoxide atmosphere. LCMS indicated complete conversion. Acetic acid (40 mL) and hydrochloric (2-methoxypropyl)hydrazine (1.3 g, 12 mmol) were added. The resultant mixture was stirred at 100° C. for 1 h. After concentration, the residue was purified by silica gel chromatography eluting with DCM/methanol (100:1) to give 12-chloro-4-[3-methyl-1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6,13-triazatricyclo[8.4.0.02,6]tetra-deca1(14),2,4,10,12-pentaene (1.4 g, 71% yield) as a white solid. LCMS (ESI) m/z: 345.3 [M+H+].

後処理

  1. concentrationAfter concentration
  2. customthe residue was purified by silica gel chromatography
  3. washeluting with DCM/methanol (100:1)

出典と根拠

ORDレコード
ord-e965352863c84ee1af302f1cca37ae5e
出典データセット
uspto-grants-2015_07
特許番号
US09090628B2

反応ノート

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