Sodium Carbonate → HCID 67053586, compound

HRID 535766Notes

Reaction equation

HRID 535766 reaction equation
Br[C:2]1([C:10]2[CH:15]=[CH:14][N:13]=[C:12]([NH:16][CH2:17][C@@H:18]([NH:20][C:21](=[O:24])[O:22][CH3:23])[CH3:19])[N:11]=2)[CH2:6][NH:5][C:4]([CH:7]2[CH2:9][CH2:8]2)=[N:3]1.[Cl:25][C:26]1[CH:27]=[C:28](B2OC(C)(C)C(C)(C)O2)[C:29]([F:33])=[C:30]([CH:32]=1)[NH2:31].C([O-])([O-])=O.[Na+].[Na+]>COCCOC.O1CCOCC1.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>[NH2:31][C:30]1[C:29]([F:33])=[C:28]([C:6]2[N:5]=[C:4]([CH:7]3[CH2:9][CH2:8]3)[NH:3][C:2]=2[C:10]2[CH:15]=[CH:14][N:13]=[C:12]([NH:16][CH2:17][C@@H:18]([NH:20][C:21](=[O:24])[O:22][CH3:23])[CH3:19])[N:11]=2)[CH:27]=[C:26]([Cl:25])[CH:32]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 574162195-Chloro-2-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline2×HCID 178502275HCID 178502275, compound

Product 1

HCID 67053586HCID 67053586, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of (S)-methyl 1-(4-(4-bromo-2-cyclopropyl-1H-imidazol-4-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate (I-1b, 0.59 g, 1.5 mmol) in DME (15 mL) was added a solution of 5-chloro-2-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (SM-5, (˜12 mL, 0.25 M solution in dioxane; 3.0 mmol) and aqueous Na2CO3 solution (6 mL, 2.0 M, 12.0 mL). The resulting mixture was sparged with nitrogen, and Pd(PPh3)4 (87 mg, 0.075 mmol) was added. The reaction mixture was sealed and subjected to microwave irradiation at 120° C. for about 20 minutes. The reaction was allowed to cool to room temperature and partitioned upon standing. The layers were separated and the organic portion was concentrated, dissolved in EtOAc (150 mL), washed with water (50 mL), followed by extraction with aqueous 0.01 M HCl solution (2×100 mL) and aqueous 0.02 M HCl solution (2×100 mL). The combined acidic aqueous portions were neutralized with saturated aqueous NaHCO3 solution, and extracted with EtOAc (2×225 mL). The combined organic portions were washed with brine, dried (Na2SO4), and concentrated to yield (S)-methyl 1-(4-(4-(3-amino-5-chloro-2-fluorophenyl)-2-cyclopropyl-1H-imidazol-5-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate (530 mg) which was carried forward without further purification. LCMS (m/z) 460.2 (MH+), tR=0.57 minute.

Workup

  1. additionwas added
  2. customThe reaction mixture was sealed
  3. customirradiation at 120° C. for about 20 minutes
  4. custompartitioned
  5. customThe layers were separated
  6. concentrationthe organic portion was concentrated
  7. dissolutiondissolved in EtOAc (150 mL)
  8. washwashed with water (50 mL)
  9. extractionfollowed by extraction with aqueous 0.01 M HCl solution (2×100 mL) and aqueous 0.02 M HCl solution (2×100 mL)
  10. extractionextracted with EtOAc (2×225 mL)
  11. washThe combined organic portions were washed with brine
  12. dry with materialdried (Na2SO4)
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-9abbe7af1bcf46028e311e58cbc2ab50
Source dataset
uspto-grants-2014_10
Patent number
US08859548B2

Reaction notes

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