1-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole → 3-(3-methoxy-4-((4-(perfluoroethyl)benzyl)oxy)benzyl)-6-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-2-amine

HRID 2178376Notes

Reaction equation

HRID 2178376 reaction equation
I[C:2]1[CH:3]=[C:4]2[N:10]=[C:9]([NH:11]C(=O)OCC)[N:8]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([O:24][CH2:25][C:26]4[CH:31]=[CH:30][C:29]([C:32]([F:38])([F:37])[C:33]([F:36])([F:35])[F:34])=[CH:28][CH:27]=4)=[C:20]([O:39][CH3:40])[CH:19]=3)[C:5]2=[N:6][CH:7]=1.[CH3:41][N:42]1[CH:46]=[C:45](B2OC(C)(C)C(C)(C)O2)[CH:44]=[N:43]1>CN(C)C=O.C(=O)([O-])[O-].[Na+].[Na+].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Cl-].[Cl-].[Fe+2].[Pd+2]>[CH3:40][O:39][C:20]1[CH:19]=[C:18]([CH:23]=[CH:22][C:21]=1[O:24][CH2:25][C:26]1[CH:31]=[CH:30][C:29]([C:32]([F:38])([F:37])[C:33]([F:36])([F:34])[F:35])=[CH:28][CH:27]=1)[CH2:17][N:8]1[C:5]2=[N:6][CH:7]=[C:2]([C:45]3[CH:44]=[N:43][N:42]([CH3:41])[CH:46]=3)[CH:3]=[C:4]2[N:10]=[C:9]1[NH2:11]

Participants

6

Reactant 2

HCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 131733019HCID 131733019, compound

Product 1

HCID 1180098253-(3-methoxy-4-((4-(perfluoroethyl)benzyl)oxy)benzyl)-6-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-2-amineYield 14%

Reagents, catalysts & solvents 3

HCID 178478645Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of ethyl (6-iodo-3-(3-methoxy-4-((4-(perfluoroethyl)benzyl)oxy)benzyl)-3H-imidazo[4,5-b]pyridin-2-yl)carbamate (0.090 g, 0.13 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.054 g, 0.26 mmol) in N,N-dimethylformamide (3 mL) and 2M aqueous sodium carbonate solution (150 μL) was added (1,1′-bis(diphenylphosphino)ferrocene)palladium(II) dichloride (0.050 g, 0.06 mmol). The resulting mixture was heated to 80° C. under a nitrogen atmosphere. After 4 h, the mixture was allowed to cool to room temperature and was filtered through Celite. The filtrate was diluted with water (10 mL) and extracted with ethyl acetate (3×20 mL). The combined organic phases were dried over sodium sulfate, filtered, and concentrated. The residue was purified by prep-HPLC to afford 0.010 g (14%) of the product as a white solid: 1H NMR (400 MHz, DMSO-d6) δ 8.10 (s, 2H), 7.84 (s, 1H), 7.72-7.70 (m, 2H), 7.66-7.64 (m, 2H), 7.58 (d, J=1.6 Hz, 1H), 7.12 (d, J=1.6 Hz, 1H), 6.95-6.89 (m, s 3H), 6.72 (d, J=6.8 Hz, 1H), 5.19 (s, 2H), 5.15 (s, 2H), 3.85 (s, 3H), 3.73 (s, 3H) ppm; (M+1)=559.

Workup

  1. temperatureto cool to room temperature
  2. filtrationwas filtered through Celite
  3. additionThe filtrate was diluted with water (10 mL)
  4. extractionextracted with ethyl acetate (3×20 mL)
  5. dry with materialThe combined organic phases were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-3d2d3b80cded49028b4ffc9a915d01bd
Source dataset
uspto-grants-2015_06
Patent number
US09067914B1

Reaction notes

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