Nitrogen → HCID 117844086, compound

HRID 2209135Notes

Reaction equation

HRID 2209135 reaction equation
[CH:1]1([N:4]2[C:8]3[C:9]([O:22][C@@H:23]([C@H:25]4[CH2:29][NH:28][C:27](=[O:30])[CH2:26]4)[CH3:24])=[CH:10][C:11](B4OC(C)(C)C(C)(C)O4)=[CH:12][C:7]=3[N:6]=[CH:5]2)[CH2:3][CH2:2]1.Br[C:32]1[S:33][C:34]([CH3:38])=[C:35]([CH3:37])[N:36]=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:1]1([N:4]2[C:8]3[C:9]([O:22][C@@H:23]([C@H:25]4[CH2:29][NH:28][C:27](=[O:30])[CH2:26]4)[CH3:24])=[CH:10][C:11]([C:32]4[S:33][C:34]([CH3:38])=[C:35]([CH3:37])[N:36]=4)=[CH:12][C:7]=3[N:6]=[CH:5]2)[CH2:3][CH2:2]1

Participants

8

Reactant 4

HCID 947NitrogenHCID 10340Sodium CarbonateHCID 99423662-Bromo-4,5-dimethylthiazoleHCID 123319683(R)-4-((R)-1-((1-cyclopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one

Product 1

HCID 117844086HCID 117844086, compoundYield 48.4%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

To a microwave tube equipped with a stifling bar, (R)-4-((R)-1-((1-cyclopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one: (120 mg, 0.292 mmol), 2-bromo-4,5-dimethylthiazole (112.1 mg, 0.584 mmol), 1,2-dimethoxyethane (2 mL), 1 N Na2CO3 aqueous solution (0.73 mL, 0.73 mmol) were added, the mixture was bubbled N2 for 5 minutes before Pd(PPh3)4 (14.0 mg, 0.012 mmol) were added. The tube was sealed and heated in an oil bath at 100° C. for 2 hrs. 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, 56.0 mg (yield 48.4%). 1H NMR (300 MHz, DMSO-d6) δ 8.15 (s, 1H), 7.59 (s, 1H), 7.58 (d, J=1.2 Hz, 1H), 7.32 (d, J=1.4 Hz, 1H), 4.79 (p, J=6.0 Hz, 1H), 3.70 (m, 1H), 3.44-3.35 (m, 1H), 3.25-3.15 (m, 1H), 2.91-2.72 (m, 1H), 2.37 (s, 3H), 2.32 (s, 3H), 2.41-2.22 (m, 2H), 1.33 (d, J=6.0 Hz, 3H), 1.16-1.07 (m, 2H), 1.07-0.97 (m, 2H) ppm; MS (ESI+) m/z 397.14 (M+H).

Workup

  1. customTo a microwave tube equipped with a stifling bar
  2. additionwere 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, 56.0 mg (yield 48.4%)

Sources & evidence

ORD record
ord-ad33521a8724407ab2a0b0e392546ad2
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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