4-Methylmorpholine → (R)-tert-Butyl 4-(3-(5-chloro-3-(3-methoxypropyl)-3H-imidazo[4,5-b]pyridin-2-yl)piperidin-1-yl)-1-(naphthalen-2-yl)-4-oxobutan-2-ylcarbamate

HRID 1096622Notes

Reaction equation

HRID 1096622 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]2[N:8]([CH2:17][CH2:18][CH2:19][O:20][CH3:21])[C:9]([CH:11]3[CH2:16][CH2:15][CH2:14][NH:13][CH2:12]3)=[N:10][C:5]2=[CH:4][CH:3]=1.[C:22]([O:26][C:27]([NH:29][C@H:30]([CH2:35][C:36]1[CH:45]=[CH:44][C:43]2[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=2)[CH:37]=1)[CH2:31][C:32](O)=[O:33])=[O:28])([CH3:25])([CH3:24])[CH3:23].CN1CCOCC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[Cl:1][C:2]1[N:7]=[C:6]2[N:8]([CH2:17][CH2:18][CH2:19][O:20][CH3:21])[C:9]([CH:11]3[CH2:16][CH2:15][CH2:14][N:13]([C:32](=[O:33])[CH2:31][C@H:30]([NH:29][C:27](=[O:28])[O:26][C:22]([CH3:23])([CH3:24])[CH3:25])[CH2:35][C:36]4[CH:45]=[CH:44][C:43]5[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=5)[CH:37]=4)[CH2:12]3)=[N:10][C:5]2=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 7021578(R)-3-((tert-butoxycarbonyl)amino)-4-(naphthalen-2-yl)butanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 867615305-chloro-3-(3-methoxypropyl)-2-(piperidin-3-yl)-3H-imidazo[4,5-b]pyridine

Product 1

HCID 86761532(R)-tert-Butyl 4-(3-(5-chloro-3-(3-methoxypropyl)-3H-imidazo[4,5-b]pyridin-2-yl)piperidin-1-yl)-1-(naphthalen-2-yl)-4-oxobutan-2-ylcarbamateYield 62%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Compound 35C (0.288 mmol, 0.122 g) was added to a 10 mL round-bottomed flask equipped for stirring under nitrogen. DMF (2 mL), (R)-3-(tert-butoxycarbonylamino)-4-(naphthalen-2-yl)butanoic acid (0.455 mmol, 0.150 g) and N-methylmorpholine (1.15 mmol, 0.127 mL) were then added and the solution was allowed to stir at it for 5 min. HATU (0.317 mmol, 0.120 g) was added and the resultant solution was stirred at room temperature for 3 hr. The reaction solution was then directly purified by preparative LC/MS (40-95% CH3CN in H2O). The resultant fractions were collected and the solvent was removed in-vacuo affording (R)-tert-Butyl 4-(3-(5-chloro-3-(3-methoxypropyl)-3H-imidazo[4,5-b]pyridin-2-yl)piperidin-1-yl)-1-(naphthalen-2-yl)-4-oxobutan-2-ylcarbamate (35D) as a clear oil (0.177 mmol, 0.110 g, 62% yield). ESI-MS: m/z 620.4 (M+H)+.

Workup

  1. customequipped
  2. stirringto stir at it for 5 min
  3. customThe reaction solution was then directly purified by preparative LC/MS (40-95% CH3CN in H2O)
  4. customThe resultant fractions were collected
  5. customthe solvent was removed in-vacuo

Sources & evidence

ORD record
ord-fff2e086854f4a96b214cbb0ca6675da
Source dataset
uspto-grants-2012_03
Patent number
US08138168B1

Reaction notes

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