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 220944노트

반응식

HRID 220944 반응식
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]

참가 물질

6

반응물 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

생성물 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)-benzylamide수율 46%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 81531Diisopropylethylamine용매

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-814eb7aad2824144a91c0ba5d3383556
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08202858B2

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