4-Methylmorpholine → tert-butyl (R)-4-((R)-3-(6-methoxy-1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-1-(naphthalen-2-yl)-4-oxobutan-2-ylcarbamate

HRID 1096631Notes

Reaction equation

HRID 1096631 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[N:10]=[C:9]([C@@H:11]3[CH2:16][CH2:15][CH2:14][NH:13][CH2:12]3)[N:8]([CH2:17][CH2:18][CH2:19][O:20][CH3:21])[C:7]=2[CH:22]=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.O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[N:10]=[C:9]([C@@H:11]3[CH2:16][CH2:15][CH2:14][N:13]([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)[CH2:12]3)[N:8]([CH2:17][CH2:18][CH2:19][O:20][CH3:21])[C:7]=2[CH:22]=1

Participants

7

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 66784136(R)-6-Methoxy-1-(3-methoxypropyl)-2-(piperidin-3-yl)-1H-benzo[d]imidazole

Product 1

HCID 66791507tert-butyl (R)-4-((R)-3-(6-methoxy-1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-1-(naphthalen-2-yl)-4-oxobutan-2-ylcarbamateYield 22.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

(R)-6-Methoxy-1-(3-methoxypropyl)-2-(piperidin-3-yl)-1H-benzo[d]imidazole (41E) (2.82 mmol, 0.86 g) in DMF (16 mL) was added (R)-3-(tert-butoxycarbonylamino)-4-(naphthalen-2-yl)butanoic acid (3.10 mmol, 1.02 g) and N-methylmorpholine (11.28 mmol, 1.24 mL). The reaction mixture was stirred at rt for 5 min and then added HATU (3.10 mmol, 1.18 g) and kept stirring at rt overnight. The reaction mixture was poured into H2O, extracted with EtOAc. The extract was washed with H2O, NaHCO3, brine, dried over MgSO4 and filtered. The filtrate was concentrated in vacuo and purified by preparative LC/MS (40-90% CH3CN in H2O) to afford tert-butyl (R)-4-((R)-3-(6-methoxy-1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-1-(naphthalen-2-yl)-4-oxobutan-2-ylcarbamate (42F) (0.63 mmol, 0.387 g, three-step yield: 22.3%). ESI-MS: m/z 616.5 (M+H)+.

Workup

  1. extractionextracted with EtOAc
  2. washThe extract was washed with H2O, NaHCO3, brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo
  6. custompurified by preparative LC/MS (40-90% CH3CN in H2O)

Sources & evidence

ORD record
ord-a3174f5bb3ff46ec9f3c523b00555c64
Source dataset
uspto-grants-2012_03
Patent number
US08138168B1

Reaction notes

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