Sodium Carbonate → HCID 117842970, compound

HRID 2209111Notes

Reaction equation

HRID 2209111 reaction equation
Br[C:2]1[N:7]=[C:6]([O:8][C@@H:9]([C@H:11]2[CH2:15][NH:14][C:13](=[O:16])[CH2:12]2)[CH3:10])[C:5]2[N:17]([CH:20]3[CH2:22][CH2:21]3)[CH:18]=[N:19][C:4]=2[CH:3]=1.CC1(C)C(C)(C)OB([C:31]2[CH:36]=[CH:35][N:34]=[CH:33][CH:32]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:20]1([N:17]2[C:5]3[C:6]([O:8][C@@H:9]([C@H:11]4[CH2:15][NH:14][C:13](=[O:16])[CH2:12]4)[CH3:10])=[N:7][C:2]([C:31]4[CH:36]=[CH:35][N:34]=[CH:33][CH:32]=4)=[CH:3][C:4]=3[N:19]=[CH:18]2)[CH2:22][CH2:21]1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27346484-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 117843105(R)-4-((R)-1-((6-bromo-3-cyclopropyl-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-on

Product 1

HCID 117842970HCID 117842970, compoundYield 52.3%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

Into a microwave reaction vial, a mixture of (R)-4-((R)-1-((6-bromo-3-cyclopropyl-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one: (100.0 mg, 0.27 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (168.4 mg, 0.82 mmol), sodium carbonate (116.0 mg, 1.10 mmol) and Pd(PPh3)4 (31.6 mg, 0.027 mmol) were placed in dioxane (4 mL) and water (1 mL). The reaction mixture was placed in the microwave reactor and heated at 150° C. for 30 min. Then, it was filtered through a pad of Celite and partitioned between EtOAc (2×30 mL) and brine (2×10 mL). The combined organic layers were washed with water (2×5 mL), concentrated, and purified by flash chromatography (100% EtOAc to 20% MeOH in EtOAc) to give 52.0 mg (52.3%) of (R)-4-((R)-1-((3-cyclopropyl-6-(pyridin-4-yl)-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one:. 1H NMR (300 MHz, DMSO-d6) δ 8.44 (dd, J=1.8, 1.2 Hz, 2H), 8.162 (s, 1H), 7.896-7.863 (m, 3H), 7.383 (s, 1H), 5.438-5.398 (m, 1H), 3.551-3.492 (m, 1H), 3.22 (t, J=9.5 Hz, 1H), 3.03 (dd, J=6.6, 6.6 Hz, 1H), 2.701-2.633 (m, 1H), 2.15 (dd, J=2.3, 1.7 Hz, 2H), 1.24 (d, J=6.5 Hz, 3H), 1.0-0.828 (m, 4H). LCMS-ESI+ (m/z): [M+H]+ calcd C20H21N5O2: 363.17; found 364.14.

Workup

  1. filtrationThen, it was filtered through a pad of Celite
  2. custompartitioned between EtOAc (2×30 mL) and brine (2×10 mL)
  3. washThe combined organic layers were washed with water (2×5 mL)
  4. concentrationconcentrated
  5. custompurified by flash chromatography (100% EtOAc to 20% MeOH in EtOAc)

Sources & evidence

ORD record
ord-16009e3ef30c411ab68d15525de2984e
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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