Diisopropylethylamine → benzyl (2-{[(4-{(3S,5R)-3-[(tert-butoxycarbonyl)amino]-5-methylpiperidin-1-yl}pyridin-3-yl)amino]carbonyl}-7-morpholin-4-ylquinolin-3-yl)carbamate

HRID 924450Notes

Reaction equation

HRID 924450 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C:12]1[C:13]([C:28](O)=[O:29])=[N:14][C:15]2[C:20]([CH:21]=1)=[CH:19][CH:18]=[C:17]([N:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1)[CH:16]=2)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:31][C:32]1[CH:33]=[N:34][CH:35]=[CH:36][C:37]=1[N:38]1[CH2:43][C@H:42]([CH3:44])[CH2:41][C@H:40]([NH:45][C:46](=[O:52])[O:47][C:48]([CH3:51])([CH3:50])[CH3:49])[CH2:39]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.CCOC(C)=O.[OH-].[Na+]>[C:48]([O:47][C:46]([NH:45][C@H:40]1[CH2:41][C@@H:42]([CH3:44])[CH2:43][N:38]([C:37]2[CH:36]=[CH:35][N:34]=[CH:33][C:32]=2[NH:31][C:28]([C:13]2[C:12]([NH:11][C:9](=[O:10])[O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[CH:21][C:20]3[C:15](=[CH:16][C:17]([N:22]4[CH2:23][CH2:24][O:25][CH2:26][CH2:27]4)=[CH:18][CH:19]=3)[N:14]=2)=[O:29])[CH2:39]1)=[O:52])([CH3:49])([CH3:50])[CH3:51]

Participants

8

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 58386794HCID 58386794, compoundHCID 867268923-{[(Benzyloxy)carbonyl]amino}-7-morpholin-4-ylquinoline-2-carboxylic acid

Product 1

HCID 86726895benzyl (2-{[(4-{(3S,5R)-3-[(tert-butoxycarbonyl)amino]-5-methylpiperidin-1-yl}pyridin-3-yl)amino]carbonyl}-7-morpholin-4-ylquinolin-3-yl)carbamate

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 14798Sodium HydroxideSolvent

Procedure

A mixture of 3-{[(benzyloxy)carbonyl]amino}-7-morpholin-4-ylquinoline-2-carboxylic acid (0.014 g, 0.034 mmol), tert-butyl [(3S,5R)-1-(3-aminopyridin-4-yl)-5-methylpiperidin-3-yl]carbamate (0.013 g, 0.041 mmol) and HATU (0.033 g, 0.086 mmol) in DMF (0.14 mL) and DIPEA (0.018 mL, 0.10 mmol) was stirred at room temperature for 2 h. The mixture was diluted with 5 mL of EtOAc and 3 mL of 1 M NaOH. The layers were separated and the aqueous layer was extracted with EtOAc. The organic layers were combined and concentrated under reduced pressure. The residue was purified by flash chromatography on 20 g silica gel column, eluting with 0-30% MeOH in EtOAc, to yield an amide intermediate, benzyl (2-{[(4-{(3S,5R)-3-[(tert-butoxycarbonyl)amino]-5-methylpiperidin-1-yl}pyridin-3-yl)amino]carbonyl}-7-morpholin-4-ylquinolin-3-yl)carbamate. LCMS calc. for C38H46N7O6 [M+H]+: m/z=696.3. found: 696.5.

Workup

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted with EtOAc
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by flash chromatography on 20 g silica gel column
  5. washeluting with 0-30% MeOH in EtOAc

Sources & evidence

ORD record
ord-61facad2c9ce439ba6cbfb389ed203e7
Source dataset
uspto-grants-2016_03
Patent number
US09278950B2

Reaction notes

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