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

HRID 1096617Notes

Reaction equation

HRID 1096617 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[C:7]2[N:9]([CH2:18][CH2:19][CH2:20][O:21][CH3:22])[C:10]([CH:12]3[CH2:17][CH2:16][CH2:15][NH:14][CH2:13]3)=[N:11][C:6]2=[CH:5][CH:4]=1.[C:23]([O:27][C:28]([NH:30][C@H:31]([CH2:36][C:37]1[CH:46]=[CH:45][C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[CH:38]=1)[CH2:32][C:33](O)=[O:34])=[O:29])([CH3:26])([CH3:25])[CH3:24].CN1CCOCC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH3:1][O:2][C:3]1[N:8]=[C:7]2[N:9]([CH2:18][CH2:19][CH2:20][O:21][CH3:22])[C:10]([CH:12]3[CH2:17][CH2:16][CH2:15][N:14]([C:33](=[O:34])[CH2:32][C@H:31]([NH:30][C:28](=[O:29])[O:27][C:23]([CH3:24])([CH3:25])[CH3:26])[CH2:36][C:37]4[CH:46]=[CH:45][C:44]5[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=5)[CH:38]=4)[CH2:13]3)=[N:11][C:6]2=[CH:5][CH:4]=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 667864945-Methoxy-3-(3-methoxypropyl)-2-(piperidin-3-yl)-3H-imidazo[4,5-b]pyridine

Product 1

HCID 66785172(R)-tert-butyl 4-(3-(5-methoxy-3-(3-methoxypropyl)-3H-imidazo[4,5-b]pyridin-2-yl)piperidin-1-yl)-1-(naphthalen-2-yl)-4-oxobutan-2-ylcarbamateYield 73%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-Methoxy-3-(3-methoxypropyl)-2-(piperidin-3-yl)-3H-imidazo[4,5-b]pyridine (33D) (0.600 mmol, 0.182 g) was added to a 15 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 (1.8 mmol, 0.198 mL) were then added and the solution was allowed to stir at rt for 5 min. HATU (0.660 mmol, 0.251 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 (35-80% CH3CN in H2O). The resultant fractions were collected and the solvent was removed in-vacuo affording (R)-tert-butyl 4-(3-(5-methoxy-3-(3-methoxypropyl)-3H-imidazo[4,5-b]pyridin-2-yl)piperidin-1-yl)-1-(naphthalen-2-yl)-4-oxobutan-2-ylcarbamate (33E) as a clear oil. (0.333 mmol, 0.205 g, 73% yield). ESI-MS: m/z 616.5 (M+H)+.

Workup

  1. customequipped
  2. stirringto stir at rt for 5 min
  3. customThe reaction solution was then directly purified by preparative LC/MS (35-80% CH3CN in H2O)
  4. customThe resultant fractions were collected
  5. customthe solvent was removed in-vacuo

Sources & evidence

ORD record
ord-97814047a93a4f6495d760b8e1739a02
Source dataset
uspto-grants-2012_03
Patent number
US08138168B1

Reaction notes

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