6-(3-cyclopropyl-4-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)-3H-imidazo[4,5-c]pyridin-6-yl)indolin-2-one → (4R)-4-((1R)-1-((6-(4-(6-oxa-3-azabicyclo[3.1.1]heptan-3-yl)phenyl)-3-cyclopropyl-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one

HRID 2209110Notes

Reaction equation

HRID 2209110 reaction equation
[CH:1]1([N:4]2[C:8]3[C:9]([O:23][C@@H:24]([C@@H:26]4[CH2:30][C:29](=[O:31])[NH:28][CH2:27]4)[CH3:25])=[N:10][C:11](C4C=C5C(CC(=O)N5)=CC=4)=[CH:12][C:7]=3[N:6]=[CH:5]2)[CH2:3][CH2:2]1.CC1(C)C(C)(C)OB([C:40]2[CH:45]=[CH:44][C:43]([N:46]3[CH2:51][CH:50]4[CH2:52][CH:48]([O:49]4)[CH2:47]3)=[CH:42][CH:41]=2)O1>>[CH:50]12[CH2:52][CH:48]([O:49]1)[CH2:47][N:46]([C:43]1[CH:42]=[CH:41][C:40]([C:11]3[N:10]=[C:9]([O:23][C@@H:24]([C@H:26]4[CH2:27][NH:28][C:29](=[O:31])[CH2:30]4)[CH3:25])[C:8]4[N:4]([CH:1]5[CH2:3][CH2:2]5)[CH:5]=[N:6][C:7]=4[CH:12]=3)=[CH:45][CH:44]=1)[CH2:51]2

Participants

3

Reactant 2

HCID 1178438396-(3-cyclopropyl-4-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)-3H-imidazo[4,5-c]pyridin-6-yl)indolin-2-oneHCID 1234126683-(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-6-oxa-3-azabicyclo[3.1.1]heptane

Product 1

HCID 117843678(4R)-4-((1R)-1-((6-(4-(6-oxa-3-azabicyclo[3.1.1]heptan-3-yl)phenyl)-3-cyclopropyl-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-oneYield 41%

Procedure

Prepared by Suzuki coupling reaction procedure, as previously described for the synthesis of 6-(3-cyclopropyl-4-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)-3H-imidazo[4,5-c]pyridin-6-yl)indolin-2-one:, using instead 3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-6-oxa-3-azabicyclo[3.1.1]heptane (123.7 mg, 0.41 mmol) to afford 51.2 mg (41%) of (4R)-4-((1R)-1-((6-(4-(6-oxa-3-azabicyclo[3.1.1]heptan-3-yl)phenyl)-3-cyclopropyl-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one:. 1H NMR (300 MHz, d6-DMSO) δ 8.21 (s, 1H), 7.96 (d, J=8.8 Hz, 2H), 7.61 (s, 1H), 7.55 (s, 1H), 6.79 (d, J=8.7 Hz, 2H), 5.57 (m, 1H), 4.71 (m, 2H), 3.50 (m, 6H), 3.21 (m, 2H), 2.83 (m, 1H), 2.32 (m, 2H), 1.91 (m, 1H), 1.39 (d, J=6.2 Hz, 3H), 1.14 (m, 4H). MS (ESI+) m/z 460.2 (M+H).

Workup

  1. customPrepared by Suzuki
  2. customreaction procedure

Sources & evidence

ORD record
ord-9d5cfa084cd54088bb40a384feaf26e7
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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