Diisopropylethylamine → 3-{[(3-{[(Benzyloxy)carbonyl]amino}-7-ethylquinolin-2-yl)carbonyl]amino}-4-{(3S)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl acetate

HRID 924406Notes

Reaction equation

HRID 924406 reaction equation
[C:1]([O:4][CH:5]1[C:9]2=[N:10][CH:11]=[C:12]([NH2:28])[C:13]([N:14]3[CH2:19][CH2:18][CH2:17][C@H:16]([NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:15]3)=[C:8]2[CH2:7][CH2:6]1)(=[O:3])[CH3:2].[CH2:29]([O:36][C:37]([NH:39][C:40]1[C:41]([C:52](O)=[O:53])=[N:42][C:43]2[C:48]([CH:49]=1)=[CH:47][CH:46]=[C:45]([CH2:50][CH3:51])[CH:44]=2)=[O:38])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[C:1]([O:4][CH:5]1[C:9]2=[N:10][CH:11]=[C:12]([NH:28][C:52]([C:41]3[C:40]([NH:39][C:37]([O:36][CH2:29][C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)=[O:38])=[CH:49][C:48]4[C:43](=[CH:44][C:45]([CH2:50][CH3:51])=[CH:46][CH:47]=4)[N:42]=3)=[O:53])[C:13]([N:14]3[CH2:19][CH2:18][CH2:17][C@H:16]([NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:15]3)=[C:8]2[CH2:7][CH2:6]1)(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 867266943-Amino-4-{(3S)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl acetateHCID 867268743-{[(Benzyloxy)carbonyl]amino}-7-ethylquinoline-2-carboxylic acid

Product 1

HCID 867268733-{[(3-{[(Benzyloxy)carbonyl]amino}-7-ethylquinolin-2-yl)carbonyl]amino}-4-{(3S)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl acetateYield 42.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 3-amino-4-{(3S)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl acetate (6.15 mg, 0.0158 mmol), 3-{[(benzyloxy)carbonyl]amino}-7-ethylquinoline-2-carboxylic acid (4.6 mg, 0.013 mmol), HATU (12.5 mg, 0.0328 mmol), DMF (0.0305 mL) and DIPEA (5.09 mg, 0.0394 mmol) was stirred at room temperature for 1 h. The reaction mixture was filtered, concentrated under reduced pressure and purified by preparative LC MS (pH=10 method; XBridge™ preparative C18 5 μm OBD™ column, 30×10 mm, 60 mL/min., eluting with a gradient of MeCN and water with NH4OH) to give pure sub-title compound as a colorless gum (4 mg, 40%). LCMS calc. for C40H47N6O7 (M+H)+: m/z=723.4. Found: 723.3.

Workup

  1. filtrationThe reaction mixture was filtered
  2. concentrationconcentrated under reduced pressure
  3. custompurified by preparative LC MS (pH=10 method
  4. washXBridge™ preparative C18 5 μm OBD™ column, 30×10 mm, 60 mL/min., eluting with a gradient of MeCN and water with NH4OH)

Sources & evidence

ORD record
ord-53daedbebfeb46ccb9679654e657dd16
Source dataset
uspto-grants-2016_03
Patent number
US09278950B2

Reaction notes

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