Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → 1-Cyclopropylmethyl-piperidine-4-carboxylic acid 3-fluoro-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide

HRID 220944ノート

反応式

HRID 220944 の反応式
CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH:25]1([CH2:28][N:29]2[CH2:34][CH2:33][CH:32]([C:35]([OH:37])=O)[CH2:31][CH2:30]2)[CH2:27][CH2:26]1.Cl.[NH2:39][CH2:40][C:41]1[CH:46]=[CH:45][C:44]([C:47]([N:49]2[CH2:58][C:57]3[CH:56]=[N:55][N:54]([CH3:59])[C:53]=3[NH:52][C:51]3[CH:60]=[CH:61][CH:62]=[CH:63][C:50]2=3)=[O:48])=[C:43]([F:64])[CH:42]=1>CN(C=O)C.CCN(C(C)C)C(C)C>[F:64][C:43]1[CH:42]=[C:41]([CH:46]=[CH:45][C:44]=1[C:47]([N:49]1[CH2:58][C:57]2[CH:56]=[N:55][N:54]([CH3:59])[C:53]=2[NH:52][C:51]2[CH:60]=[CH:61][CH:62]=[CH:63][C:50]1=2)=[O:48])[CH2:40][NH:39][C:35]([CH:32]1[CH2:31][CH2:30][N:29]([CH2:28][CH:25]2[CH2:26][CH2:27]2)[CH2:34][CH2:33]1)=[O:37]

参加物

6

反応物 3

HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 162440151-(Cyclopropylmethyl)piperidine-4-carboxylic acidHCID 136346643(4-Aminomethyl-2-fluoro-phenyl)-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulen-9-yl)-methanone Hydrochloride

生成物 1

HCID 1361284301-Cyclopropylmethyl-piperidine-4-carboxylic acid 3-fluoro-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide収率 46%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 81531Diisopropylethylamine溶媒

実験手順

HBTU (227 mg, 0.6 mmol) was added to a solution of 1-cyclopropylmethyl-piperidine-4-carboxylic acid from Example E15a (99 mg, 0.45 mmol) in DMF (5 ml) and DIEA (to pH9). The mixture was stirred at room temperature for 1 h. (4-Aminomethyl-2-fluoro-phenyl)-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulen-9-yl)-methanone hydrochloride from Example E90.2 (116 mg, 0.3 mmol) was added and the mixture was stirred at room temperature for 18 h. Solvents were removed in vacuo and azeotroped with toluene. The residue was redissolved in EtOAc, washed with saturated NaHCO3 then brine, dried and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (eluant; 1% 35% ammonia:19% methanol:80% dichloromethane) to give a white solid identified as the title compound (71.5 mg, 46%).

後処理

  1. additionwas added
  2. customSolvents were removed in vacuo
  3. customazeotroped with toluene
  4. dissolutionThe residue was redissolved in EtOAc
  5. washwashed with saturated NaHCO3
  6. dry with materialbrine, dried
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography on silica gel (eluant; 1% 35% ammonia:19% methanol:80% dichloromethane)
  9. customto give a white solid

出典と根拠

ORDレコード
ord-814eb7aad2824144a91c0ba5d3383556
出典データセット
uspto-grants-2012_06
特許番号
US08202858B2

反応ノート

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