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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
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HRID 1091564 반응식
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
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참가 물질

6

반응물 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

생성물 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
수율 95%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

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.

후처리

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

출처 및 근거

ORD 기록
ord-292904a4dbb14e719e8079969ddbf6ee
출처 데이터셋
uspto-grants-2012_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08129367B2

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