Diisopropylethylamine → 13-cyclohexyl-6-(1-cyclopropyl-4-(((2R,6S)-2,6-dimethyl-4-morpholinyl)carbonyl)-3-isopropyl-1H-pyrazol-5-yl)-N-(isopropylsulfonyl)-3-methoxy-7H-indolo[2,1-a][2]benzazepine-10-carboxamide

HRID 1094543Notes

Reaction equation

HRID 1094543 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH:25]1([C:31]2[C:32]3[CH:33]=[CH:34][C:35]([C:65](=[O:73])[NH:66][S:67]([CH:70]([CH3:72])[CH3:71])(=[O:69])=[O:68])=[CH:36][C:37]=3[N:38]3[CH2:44][C:43]([C:45]4[N:49]([CH:50]5[CH2:52][CH2:51]5)[N:48]=[C:47]([CH:53]([CH3:55])[CH3:54])[C:46]=4[C:56]([OH:58])=O)=[CH:42][C:41]4[CH:59]=[C:60]([O:63][CH3:64])[CH:61]=[CH:62][C:40]=4[C:39]=23)[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1.[CH3:74][C@H:75]1[O:80][C@@H:79]([CH3:81])[CH2:78][NH:77][CH2:76]1.CCN(C(C)C)C(C)C>CN(C=O)C>[CH:25]1([C:31]2[C:32]3[CH:33]=[CH:34][C:35]([C:65]([NH:66][S:67]([CH:70]([CH3:72])[CH3:71])(=[O:69])=[O:68])=[O:73])=[CH:36][C:37]=3[N:38]3[CH2:44][C:43]([C:45]4[N:49]([CH:50]5[CH2:52][CH2:51]5)[N:48]=[C:47]([CH:53]([CH3:55])[CH3:54])[C:46]=4[C:56]([N:77]4[CH2:76][C@H:75]([CH3:74])[O:80][C@H:79]([CH3:81])[CH2:78]4)=[O:58])=[CH:42][C:41]4[CH:59]=[C:60]([O:63][CH3:64])[CH:61]=[CH:62][C:40]=4[C:39]=23)[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 6415002,6-Dimethylmorpholine, cis-HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 579537375-(13-cyclohexyl-10-((isopropylsulfonyl)carbamoyl)-3-methoxy-7H-indolo[2,1-a][2]benzazepin-6-yl)-1-cyclopropyl-3-isopropyl-1H-pyrazole-4-carboxylic acid

Product 1

HCID 5795377113-cyclohexyl-6-(1-cyclopropyl-4-(((2R,6S)-2,6-dimethyl-4-morpholinyl)carbonyl)-3-isopropyl-1H-pyrazol-5-yl)-N-(isopropylsulfonyl)-3-methoxy-7H-indolo[2,1-a][2]benzazepine-10-carboxamideYield 31%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

HATU (65.0 mg, 0.171 mmol) was added to a stirring solution of 5-(13-cyclohexyl-10-((isopropylsulfonyl)carbamoyl)-3-methoxy-7H-indolo[2,1-a][2]benzazepin-6-yl)-1-cyclopropyl-3-isopropyl-1H-pyrazole-4-carboxylic acid (78 mg, 0.114 mmol), cis-2,6-dimethylmorpholine (28 μL, 0.23 mmol), DIEA (80 μL, 0.456 mmol) in DMF (1 mL) at room temperature. The reaction was allowed to stir for 2 hours. The reaction was purified by preparative reverse phase HPLC on a C18 column using a TFA buffered H2O/CH3CN gradient, and concentrated to give the titled compound (28 mg, 0.035 mmol, 31% yield) consistent by LCMS and NMR, with sufficient purity by HPLC.

Workup

  1. customThe reaction was purified by preparative reverse phase HPLC on a C18 column
  2. concentrationconcentrated

Sources & evidence

ORD record
ord-4b36cea4f9414ff297fa2010296b56d9
Source dataset
uspto-grants-2012_03
Patent number
US08133884B2

Reaction notes

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