4-Methylmorpholine → tert-butyl (R)-4-((R)-3-(1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-1-(naphthalen-2-yl)-4-oxobutan-2-ylcarbamate

HRID 1096606Notes

Reaction equation

HRID 1096606 reaction equation
Cl[C:2]1[C:7]2[N:8]([CH2:17][CH2:18][CH2:19][O:20][CH3:21])[C:9]([C@@H:11]3[CH2:16][CH2:15][CH2:14][NH:13][CH2:12]3)=[N:10][C:6]=2[CH:5]=[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>[CH3:21][O:20][CH2:19][CH2:18][CH2:17][N:8]1[C:7]2[CH:2]=[CH:3][CH:4]=[CH:5][C:6]=2[N:10]=[C:9]1[C@@H:11]1[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]2[CH:45]=[CH:44][C:43]3[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=3)[CH:37]=2)[CH2:12]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 66786365(R)-7-Chloro-1-(3-methoxypropyl)-2-(piperidin-3-yl)-1H-benzo[d]imidazole

Product 1

HCID 66791589tert-butyl (R)-4-((R)-3-(1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-1-(naphthalen-2-yl)-4-oxobutan-2-ylcarbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

((R)-7-chloro-1-(3-methoxypropyl)-2-(piperidin-3-yl)-1H-benzo[d]imidazole (0.111 mmol max, about half of crude oil from Step E) 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 (0.122 mmol, 0.040 g) and N-methylmorpholine (0.555 mmol, 0.061 mL) were then added and the solution was allowed to stir at rt for 5 min. HATU (0.122 mmol, 0.046 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 (20-85% CH3CN in H2O). The resultant fractions were collected and the solvent was removed in-vacuo affording tert-butyl (R)-4-((R)-3-(1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-1-(naphthalen-2-yl)-4-oxobutan-2-ylcarbamate (30F) as a clear oil that was used directly onto the next step. ESI-ESI-MS: m/z 619.5 (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 (20-85% CH3CN in H2O)
  4. customThe resultant fractions were collected
  5. customthe solvent was removed in-vacuo

Sources & evidence

ORD record
ord-2d8bde312cc8451fbf70e891f0fa7e0d
Source dataset
uspto-grants-2012_03
Patent number
US08138168B1

Reaction notes

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