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 → (R)-3-amino-1((R)-3-(6-methoxy-1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-4-(naphthalen-2-yl)butan-1-one

HRID 1096632Notes

Reaction equation

HRID 1096632 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][N:13]([C:17](=[O:39])[CH2:18][C@H:19]([NH:31]C(=O)OC(C)(C)C)[CH2:20][C:21]4[CH:30]=[CH:29][C:28]5[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=5)[CH:22]=4)[CH2:12]3)[N:8]([CH2:40][CH2:41][CH2:42][O:43][CH3:44])[C:7]=2[CH:45]=1>C(Cl)Cl>[NH2:31][C@H:19]([CH2:20][C:21]1[CH:30]=[CH:29][C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:22]=1)[CH2:18][C:17]([N:13]1[CH2:14][CH2:15][CH2:16][C@@H:11]([C:9]2[N:8]([CH2:40][CH2:41][CH2:42][O:43][CH3:44])[C:7]3[CH:45]=[C:3]([O:2][CH3:1])[CH:4]=[CH:5][C:6]=3[N:10]=2)[CH2:12]1)=[O:39]

Participants

3

Reactant 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-ylcarbamate

Product 1

HCID 66785529(R)-3-amino-1((R)-3-(6-methoxy-1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-4-(naphthalen-2-yl)butan-1-oneYield 7.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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, 387 mg) in DCM (15 mL) was added TEA (3 mL). The reaction solution was stirred at rt for 1 hr and then concentrated in vacuo. The residue was purified by preparative LC/MS (20-50% CH3CN in H2O) to afford (R)-3-amino-1((R)-3-(6-methoxy-1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-4-(naphthalen-2-yl)butan-1-one (110) (0.05 mmol, 27 mg, yield: 7.9%). ESI-MS: m/z 515.5 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.38-1.56 (m, 1H) 1.72-1.99 (m, 4H) 2.01-2.21 (m, 2H) 2.58-2.77 (m, 3H) 2.87-2.98 (m, 1H) 3.01-3.25 (m, 7H) 3.37 (t, J=5.75 Hz, 2H) 3.82 (d, 0.1=10.23 Hz, 2H) 3.88 (d, J=7.07 Hz, 3H) 4.05-4.69 (m, 3H) 7.04-7.12 (m, 1H) 7.35 (d, J=13.07 Hz, 1H) 7.45 (dd, J=8.46, 2.72 Hz, 1H) 7.48-7.55 (m, 2H) 7.64 (t, J=9.69 Hz, 1H) 7.80 (d, J=6.06 Hz, 1H) 7.83-8.03 (m, 3H).

Workup

  1. concentrationconcentrated in vacuo
  2. customThe residue was purified by preparative LC/MS (20-50% CH3CN in H2O)

Sources & evidence

ORD record
ord-24902e5d48f44fe5b932604e501b0bf5
Source dataset
uspto-grants-2012_03
Patent number
US08138168B1

Reaction notes

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