Water → HCID 117843115, compound

HRID 2209157Notes

Reaction equation

HRID 2209157 reaction equation
Br[C:2]1[N:7]=[C:6]([O:8][CH2:9][C@H:10]2[CH2:14][NH:13][C:12](=[O:15])[CH2:11]2)[C:5]2[N:16]([CH:19]3[CH2:21][CH2:20]3)[CH:17]=[N:18][C:4]=2[CH:3]=1.[O:22]1[CH2:25][CH:24]([N:26]2[CH2:31][CH2:30][N:29]([C:32]3[CH:37]=[CH:36][C:35](B4OC(C)(C)C(C)(C)O4)=[CH:34][CH:33]=3)[CH2:28][CH2:27]2)[CH2:23]1.C(=O)([O-])[O-].[Cs+].[Cs+].O>O1CCOCC1>[CH:19]1([N:16]2[C:5]3[C:6]([O:8][CH2:9][C@H:10]4[CH2:14][NH:13][C:12](=[O:15])[CH2:11]4)=[N:7][C:2]([C:35]4[CH:36]=[CH:37][C:32]([N:29]5[CH2:30][CH2:31][N:26]([CH:24]6[CH2:25][O:22][CH2:23]6)[CH2:27][CH2:28]5)=[CH:33][CH:34]=4)=[CH:3][C:4]=3[N:18]=[CH:17]2)[CH2:21][CH2:20]1

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 117843060HCID 117843060, compoundHCID 123443518HCID 123443518, compound

Product 1

HCID 117843115HCID 117843115, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

(R)-4-(((6-bromo-3-cyclopropyl-3H-imidazo[4,5-c]pyridin-4-yl)oxy)methyl)pyrrolidin-2-one (50 mg, 0.14 mmol), 1-(oxetan-3-yl)-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine (63.28 mg, 0.18 mmol), Cesium Carbonate (137.18 mg, 0.42 mmol), & PEPPSI″-IPr catalyst (20 mg, 0.03 mmol) were taken up in dioxane (4 ml) and water (1 mL) and heated in a sealed tube at 100° C. for 45 minutes. Reaction was then chromatographed in silica gel 0-30% DCM/MeOH providing 94 mg of (R)-4-(((3-cyclopropyl-6-(4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)-3H-imidazo[4,5-c]pyridin-4-yl)oxy)methyl)pyrrolidin-2-one. (68 mg, 84%) as a yellow solid: 1H NMR (300 MHz, DMSO-d6) δ 8.25 (s, 1H), 8.01-7.91 (m, 2H), 7.71-7.57 (m, 2H), 7.05-6.95 (m, 2H), 5.82-5.64 (m, 2H), 4.63-4.34 (m, 6H), 3.69 (td, J=7.0, 3.5 Hz, 1H), 3.55-3.34 (m, 2H), 3.37-3.12 (m, 9H), 2.98 (p, J=7.9 Hz, 1H), 2.50-2.32 (m, 6H), 2.20 (dd, J=16.7, 7.0 Hz, 1H), 1.27-0.97 (m, 6H). ESI MS m/z 489 [M+H]+; HPLC, 1.24 min, 97.5% (AUC).

Workup

  1. customReaction
  2. customwas then chromatographed in silica gel 0-30% DCM/MeOH providing 94 mg of (R)-4-(((3-cyclopropyl-6-(4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)-3H-imidazo[4,5-c]pyridin-4-yl)oxy)methyl)pyrrolidin-2-one
  3. customHPLC, 1.24 min, 97.5% (AUC)

Sources & evidence

ORD record
ord-5c2f761ac1cb41e2bda125ab6442b2c1
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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