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Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → tert-butyl 13-cyclohexyl-3-methoxy-6-((3-methyl-3,8-diazabicyclo[3.2.1]oct-8-yl)carbonyl)-7H-indolo[2,1-a][2]benzazepine-10-carboxylate

HRID 1091564
ノート
印刷プレビュー

反応式

HRID 1091564 の反応式
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:25]([O:29][C:30]([C:32]1[CH:33]=[CH:34][C:35]2[C:36]([CH:55]3[CH2:60][CH2:59][CH2:58][CH2:57][CH2:56]3)=[C:37]3[C:43]4[CH:44]=[CH:45][C:46]([O:48][CH3:49])=[CH:47][C:42]=4[CH:41]=[C:40]([C:50]([OH:52])=O)[CH2:39][N:38]3[C:53]=2[CH:54]=1)=[O:31])([CH3:28])([CH3:27])[CH3:26].Cl.Cl.[CH3:63][N:64]1[CH2:70][CH:69]2[NH:71][CH:66]([CH2:67][CH2:68]2)[CH2:65]1>CN(C=O)C.O>[CH:55]1([C:36]2[C:35]3[CH:34]=[CH:33][C:32]([C:30]([O:29][C:25]([CH3:26])([CH3:27])[CH3:28])=[O:31])=[CH:54][C:53]=3[N:38]3[CH2:39][C:40]([C:50]([N:71]4[CH:66]5[CH2:67][CH2:68][CH:69]4[CH2:70][N:64]([CH3:63])[CH2:65]5)=[O:52])=[CH:41][C:42]4[CH:47]=[C:46]([O:48][CH3:49])[CH:45]=[CH:44][C:43]=4[C:37]=23)[CH2:56][CH2:57][CH2:58][CH2:59][CH2:60]1
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 229243503-Methyl-3,8-diazabicyclo(3.2.1)octane--hydrogen chloride (1/2)HCID 5771220210-(tert-butoxycarbonyl)-13-cyclohexyl-3-methoxy-7H-indolo[2,1-a][2]benzazepine-6-carboxylic acid

生成物 1

HCID 57639127tert-butyl 13-cyclohexyl-3-methoxy-6-((3-methyl-3,8-diazabicyclo[3.2.1]oct-8-yl)carbonyl)-7H-indolo[2,1-a][2]benzazepine-10-carboxylate
収率 95%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

HATU (680 mg, 1.8 mmol) was added to a stirring solution of 10-(tert-butoxycarbonyl)-13-cyclohexyl-3-methoxy-7H-indolo[2,1-a][2]benzazepine-6-carboxylic acid (670 mg, 1.37 mmol) and 3-methyl-3,8-diazabicyclo[3.2.1]octane di HCl salt (560 mg, 2.81 mmol) in DMF (6 mL) and TEA (1.2 mL, 8.2 mmol) and the reaction was stirred for 30 min (complete by LCMS). The reaction mixture was diluted with water (˜35 mL) (precipitate formed) and stirred ON. The precipitate was collected by filtration, flushed with water and dried under high vacuum at 55° C. to yield tert-butyl 13-cyclohexyl-3-methoxy-6-((3-methyl-3,8-diazabicyclo[3.2.1]oct-8-yl)carbonyl)-7H-indolo[2,1-a][2]benzazepine-10-carboxylate (775 mg, 1.30 mmol, 95% yield) as a light yellow solid. The material was used without further purification. 1H NMR (300 MHz, CDCl3) δ ppm 1.14-3.95 (m, 24H), 1.59 (s, 9H), 3.86 (s, 3H), 4.21-5.26 (m, 2H), 6.82 (s, 1H), 6.88 (d, J=2.6 Hz, 1H), 7.01 (dd, J=8.8, 2.6 Hz, 1H), 7.47 (d, J=8.8 Hz, 1H), 7.66 (dd, J=8.4, 1.1 Hz, 1H), 7.80 (d, J=8.4 Hz, 1H), 8.02 (br s, 1H). LC-MS retention time: 3.72 min; m/z 596 (MH+). LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna 10 u C18 3.0×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 5 mL/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 4 min, a hold time of 1 min, and an analysis time of 5 min where solvent A was 10% MeOH/90% H2O/0.1% trifluoroacetic acid and solvent B was 10% H2O/90% MeOH/0.1% trifluoroacetic acid. MS data was determined using a Micromass Platform for LC in electrospray mode.

後処理

  1. stirringstirred ON
  2. filtrationThe precipitate was collected by filtration
  3. customflushed with water
  4. customdried under high vacuum at 55° C.

出典と根拠

ORDレコード
ord-292904a4dbb14e719e8079969ddbf6ee
出典データセット
uspto-grants-2012_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08129367B2

反応ノート

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