2-(4-(Difluoromethoxy)-3-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane → (R)-4-((R)-1-((3-cyclopropyl-6-(4-(difluoromethoxy)-3-methoxyphenyl)-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one

HRID 2209124Notes

Reaction equation

HRID 2209124 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])=[N:10][C:11](C4C=CN=CC=4)=[CH:12][C:7]=3[N:6]=[CH:5]2)[CH2:3][CH2:2]1.[F:28][CH:29]([F:48])[O:30][C:31]1[CH:36]=[CH:35][C:34](B2OC(C)(C)C(C)(C)O2)=[CH:33][C:32]=1[O:46][CH3:47]>>[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])=[N:10][C:11]([C:34]4[CH:35]=[CH:36][C:31]([O:30][CH:29]([F:28])[F:48])=[C:32]([O:46][CH3:47])[CH:33]=4)=[CH:12][C:7]=3[N:6]=[CH:5]2)[CH2:2][CH2:3]1

Participants

3

Reactant 2

HCID 584523612-(4-(Difluoromethoxy)-3-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 117842970HCID 117842970, compound

Product 1

HCID 117842685(R)-4-((R)-1-((3-cyclopropyl-6-(4-(difluoromethoxy)-3-methoxyphenyl)-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-oneYield 39.8%

Procedure

Prepared by Suzuki coupling reaction procedure, as previously described for the synthesis of (R)-4-((R)-1-((3-cyclopropyl-6-(pyridin-4-yl)-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one:, using instead 2-(4-(difluoromethoxy)-3-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (123.3 mg, 0.411 mmol) as a starting material to afford 50.0 mg (39.8%) of (R)-4-((R)-1-((3-cyclopropyl-6-(4-(difluoromethoxy)-3-methoxyphenyl)-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one:. 1H NMR (300 MHz, DMSO-d6) δ 8.28 (s, 1H), 7.88 (s, 1H), 7.81 (d, J=1.5 Hz, 1H), 7.68 (dd, J=1.8, 2.4 Hz, 1H), 7.55 (s, 1H), 7.21 (d, J=8.4 Hz, 1H). 7.07 (t, J=75 Hz, 1H), 5.58-5.50 (m, 1H), 3.92 (s, 3H), 3.72-3.65 (m, 1H), 3.39 (t, J=9.5 Hz, 1H), 3.20 (dd, J=4.8, 6.9 Hz, 1H), 2.88-2.81 (m, 1H), 2.34-2.28 (m, 2H), 1.41 (d, J=5.7 Hz, 3H), 1.11-0.99 (m, 4H), LCMS-ESI+ (m/z): [M+H]+ calcd for C23H24F2N4O4:458.18; found 459.09.

Workup

  1. customPrepared by Suzuki
  2. customreaction procedure

Sources & evidence

ORD record
ord-f9997f9933da48cd928b38e7148881c7
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

Loading…