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

HRID 1096670Notes

Reaction equation

HRID 1096670 reaction equation
[CH3:1][C:2]1[N:6]([CH:7]2[CH2:12][CH2:11][CH2:10][NH:9][CH2:8]2)[C:5]2[CH:13]=[CH:14][CH:15]=[CH:16][C:4]=2[N:3]=1.[C:17]([O:21][C:22]([NH:24][C@H:25]([CH2:30][C:31]1[CH:40]=[CH:39][C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH:32]=1)[CH2:26][C:27](O)=[O:28])=[O:23])([CH3:20])([CH3:19])[CH3:18].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][C:2]1[N:6]([CH:7]2[CH2:12][CH2:11][CH2:10][N:9]([C:27](=[O:28])[CH2:26][C@H:25]([NH:24][C:22](=[O:23])[O:21][C:17]([CH3:18])([CH3:19])[CH3:20])[CH2:30][C:31]3[CH:40]=[CH:39][C:38]4[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=4)[CH:32]=3)[CH2:8]2)[C:5]2[CH:13]=[CH:14][CH:15]=[CH:16][C:4]=2[N: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 450738432-methyl-1-(piperidin-3-yl)-1H-benzo[d]imidazole

Product 1

HCID 66786917(R)-tert-butyl 4-(3-(2-methyl-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)-1-(naphthalen-2-yl)-4-oxobutan-2-ylcarbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(2-methyl-1-(piperidin-3-yl)-1H-benzo[d]imidazole (0.486 mmoles, 0.160 g) was added to a 10 mL round-bottomed flask equipped for stirring under nitrogen. DMF (4 mL), (R)-3-(tert-butoxycarbonylamino)-4-(naphthalen-2-yl)butanoic acid (0.486 mmoles, 0.140 g) and N-methylmorpholine (1.94 mmoles, 0.214 mL) were then added and the solution was allowed to stir at rt for 5 min. HATU (0.534 mmoles, 0.204 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 (35-95% CH3CN in H2O). The resultant fractions were collected and the solvent was removed in-vacuo affording (R)-tert-butyl 4-(3-(2-methyl-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)-1-(naphthalen-2-yl)-4-oxobutan-2-ylcarbamate (1354) as a clear oil. ESI-MS: raiz 527.5 (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 (35-95% CH3CN in H2O)
  4. customThe resultant fractions were collected
  5. customthe solvent was removed in-vacuo

Sources & evidence

ORD record
ord-410b5f5d46df420582ed71f1e6b51703
Source dataset
uspto-grants-2012_03
Patent number
US08138168B1

Reaction notes

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