Sodium Carbonate → HCID 67053539, compound

HRID 885761Notes

Reaction equation

HRID 885761 reaction equation
Br[C:2]1[N:3]=[C:4]([CH:26]2[CH2:28][CH2:27]2)[N:5]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[C:6]=1[C:7]1[CH:12]=[CH:11][N:10]=[C:9]([NH:13][CH2:14][CH2:15][C:16]#[N:17])[N:8]=1.[Cl:29][C:30]1[CH:31]=[C:32](B2OC(C)(C)C(C)(C)O2)[C:33]([F:37])=[C:34]([CH:36]=1)[NH2:35].C([O-])([O-])=O.[Na+].[Na+]>COCCOC>[NH2:35][C:34]1[C:33]([F:37])=[C:32]([C:2]2[N:3]=[C:4]([CH:26]3[CH2:28][CH2:27]3)[N:5]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[C:6]=2[C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][CH2:14][CH2:15][C:16]#[N:17])[N:8]=2)[CH:31]=[C:30]([Cl:29])[CH:36]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 574162195-Chloro-2-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline2×HCID 67053594HCID 67053594, compound

Product 1

HCID 67053539HCID 67053539, compound

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

Two separate reaction vials were each charged with 3-(4-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)pyrimidin-2-ylamino)propanenitrile (I-1c, ˜200 mg, 0.43 mmol), a solution of 5-chloro-2-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (0.2 M in dioxane, 8 mL, 1.6 mmol), DME (8 mL) and aqueous 2.0 M Na2CO3 solution (2.3 mL, 4.6 mmol). The resulting mixture was sparged with Argon and Pd(PPh3)4 was added. The reaction vials were sealed and irradiated at 120° C. for 20 minutes in a microwave reactor. LCMS indicated near complete conversion. Additional 5-chloro-2-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (0.2 M in dioxane, 8 mL, 1.6 mmol) was added and the reaction was irradiated at 120° C. for 7 minutes. The reactions were allowed to cool to room temperature which partitioned upon standing. The layers were separated and the organic portions of the two reactions were combined and concentrated. The resulting residue was partitioned between EtOAc (200 mL) and water (20 mL). The layers were separated and the organic portion was washed with aqueous 0.1 N HCl solution (40 mL), brine, dried (Na2SO4), and concentrated to give 3-(4-(4-(3-amino-5-chloro-2-fluorophenyl)-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)pyrimidin-2-ylamino)propanenitrile as a crude residue which was carried forward without further purification: LCMS(m/z) 528.2 (MH+), tR=0.90 minute.

Workup

  1. customTwo separate
  2. customreaction vials
  3. customThe resulting mixture was sparged with Argon and Pd(PPh3)4
  4. additionwas added
  5. customThe reaction vials
  6. customwere sealed
  7. customirradiated at 120° C. for 20 minutes in a microwave reactor
  8. customthe reaction was irradiated at 120° C. for 7 minutes
  9. custompartitioned
  10. customThe layers were separated
  11. concentrationconcentrated
  12. customThe resulting residue was partitioned between EtOAc (200 mL) and water (20 mL)
  13. customThe layers were separated
  14. washthe organic portion was washed with aqueous 0.1 N HCl solution (40 mL), brine
  15. dry with materialdried (Na2SO4)
  16. concentrationconcentrated

Sources & evidence

ORD record
ord-953c7220875c48d2968b96090eac6310
Source dataset
uspto-grants-2012_08
Patent number
US08242260B2

Reaction notes

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