Nitrogen → (R)-4-((R)-1-((3-cyclopropyl-6-(2-methylthiazol-5-yl)-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one

HRID 2209150Notes

Reaction equation

HRID 2209150 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.[CH3:23][C:24]1[S:25][C:26](B2OC(C)(C)C(C)(C)O2)=[CH:27][N:28]=1.C([O-])([O-])=O.[Na+].[Na+].N#N>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.C(Cl)Cl.COCCOC>[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:26]4[S:25][C:24]([CH3:23])=[N:28][CH:27]=4)=[CH:3][C:4]=3[N:19]=[CH:18]2)[CH2:22][CH2:21]1

Participants

8

Reactant 4

HCID 947NitrogenHCID 10340Sodium CarbonateHCID 457858292-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-thiazoleHCID 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 117843789(R)-4-((R)-1-((3-cyclopropyl-6-(2-methylthiazol-5-yl)-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-oneYield 14.6%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
140 °C

Procedure

To a microwave tube equipped with a stirring bar, (R)-4-((R)-1-((6-bromo-3-cyclopropyl-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one: (100 mg, 0.274 mmol), 2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiazole (184.9 mg, 0.821 mmol), 1,2-dimethoxyethane (1.1 mL), 1 N Na2CO3 aqueous solution (0.82 mL, 0.82 mmol) were added, the mixture was bubbled N2 for 5 minutes before Pd(PPh3)4 (31.6 mg, 0.027 mmol) was added. The tube was sealed and heated in a microwave at 140° C. for 20 minutes. DCM (200 mL) was added and the resulting mixture was washed with saturated NaHCO3 aqueous solution (20 mL×4), brine (20 mL×1), dried over anhydrous Na2SO4, filtered, removed solvents in vacuo. The resulting residue was passed a ISCO silica gel column (MeOH:DCM=5:95) to give off-white solids, 15.3 mg (yield 14.6%). 1H NMR (300 MHz, DMSO-d6) δ 8.31 (s, 1H), 8.21 (s, 1H), 7.77 (s, 1H), 7.57 (broad s, 1H), 5.41 (p, J=6.0 Hz, 1H), 3.70-3.65 (m, 1H), 3.44-3.38 (m, 1H), 3.22-3.16 (m, 1H), 2.94-2.75 (m, 1H), 2.65 (s, 3H), 2.32 (dd, J=8.6, 2.3 Hz, 2H), 1.40 (d, J=6.1 Hz, 3H), 1.20-1.11 (m, 2H), 1.10-1.02 (m, 2H) ppm; MS (ESI+) m/z 384 (M+H).

Workup

  1. customTo a microwave tube equipped with a stirring bar
  2. additionwas added
  3. customThe tube was sealed
  4. washthe resulting mixture was washed with saturated NaHCO3 aqueous solution (20 mL×4), brine (20 mL×1)
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. customremoved solvents in vacuo
  8. customto give off-white solids, 15.3 mg (yield 14.6%)

Sources & evidence

ORD record
ord-dcc60dd45e574334bafef4aa499c708e
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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