(R)-4-((R)-1-((1-cyclopropyl-5-phenyl-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one → (R)-4-((R)-1-((1-cyclopropyl-5-(3-ethoxy-4-methoxyphenyl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one

HRID 2209118Notes

Reaction equation

HRID 2209118 reaction equation
[CH:1]1([N:4]2[C:8]3[C:9]([O:19][C@@H:20]([C@H:22]4[CH2:26][NH:25][C:24](=[O:27])[CH2:23]4)[CH3:21])=[CH:10][C:11](C4C=CC=CC=4)=[CH:12][C:7]=3[N:6]=[CH:5]2)[CH2:3][CH2:2]1.[CH2:28]([O:30][C:31]1[CH:32]=[C:33](B2OC(C)(C)C(C)(C)O2)[CH:34]=[CH:35][C:36]=1[O:37][CH3:38])[CH3:29]>>[CH:1]1([N:4]2[C:8]3[C:9]([O:19][C@@H:20]([C@H:22]4[CH2:26][NH:25][C:24](=[O:27])[CH2:23]4)[CH3:21])=[CH:10][C:11]([C:33]4[CH:34]=[CH:35][C:36]([O:37][CH3:38])=[C:31]([O:30][CH2:28][CH3:29])[CH:32]=4)=[CH:12][C:7]=3[N:6]=[CH:5]2)[CH2:2][CH2:3]1

Participants

3

Reactant 2

HCID 117843244(R)-4-((R)-1-((1-cyclopropyl-5-phenyl-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-oneHCID 1317359772-(3-Ethoxy-4-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Product 1

HCID 117843617(R)-4-((R)-1-((1-cyclopropyl-5-(3-ethoxy-4-methoxyphenyl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-oneYield 42.7%

Procedure

Prepared by Suzuki coupling reaction procedure, as previously described for the synthesis of (R)-4-((R)-1-((1-cyclopropyl-5-phenyl-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one:, using instead 2-(3-ethoxy-4-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (106.3 mg, 0.411 mmol) as a starting material to afford 51.0 mg (42.7%) of (R)-4-((R)-1-((1-cyclopropyl-5-(3-ethoxy-4-methoxyphenyl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one:. 1H NMR (300 MHz, DMSO-d6) δ 8.058 (s, 1H), 7.576 (s, 1H), 7.367 (d, J=1.2 Hz 1H), 7.184 (s, 1H), 7.155 (d, J=1.8 Hz, 1H). 6.99 (t, J=4.4 Hz 2H), 4.84 (t J=5.9 Hz, 1H), 4.11 (dd, J=7.2, 6.6 Hz, 2H), 3.768 (s, 3H), 3.709-3.637 (m, 1H), 3.38 (t, J=9 Hz, 1H) 3.18 (dd, J=6.9, 9.3 Hz, 1H), 2.83-2.75 (m, 1H), 2.379-2.207 (m, 2H), 1.358-1.282 (m, 6H), 1.125-1.00 (m, 4H). LCMS-ESI+ (m/z): [M+H]+ calcd for C25H29N3O4:435.22; found 436.18.

Workup

  1. customPrepared by Suzuki
  2. customreaction procedure

Sources & evidence

ORD record
ord-25e3c56e641845949e2b70b2b60f9a06
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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