Sodium Carbonate → HCID 67239791, compound

HRID 1028143Notes

Reaction equation

HRID 1028143 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:6]=[C:7](B2OC(C)(C)C(C)(C)O2)[CH:8]=1)[NH2:5].Br[C:19]1[S:23][C:22]([N:24]2[CH2:30][CH2:29][CH2:28][NH:27][C:26](=[O:31])[CH2:25]2)=[N:21][C:20]=1[Cl:32].C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[NH2:5][C:4]1[CH:6]=[C:7]([C:19]2[S:23][C:22]([N:24]3[CH2:30][CH2:29][CH2:28][NH:27][C:26](=[O:31])[CH2:25]3)=[N:21][C:20]=2[Cl:32])[CH:8]=[C:2]([CH3:1])[CH:3]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 672361713-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline2×HCID 67241539HCID 67241539, compound

Product 1

HCID 67239791HCID 67239791, compoundYield 55.6%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (preparation described in Intermediate XIX (1), 59 mg, 0.253 mmol), 4-(5-bromo-4-chloro-1,3-thiazol-2-yl)-1,4-diazepan-2-one (75 mg, 0.241 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride (35 mg, 0.048 mmol) in dioxane (0.600 mL) was added 2M aqueous sodium carbonate (0.240 mL, 0.480 mmol). The mixture was heated on a reaction block at 100° C. for 3 hours, and subsequently cooled to room temperature. The dark mixture was filtered through a celite plug, which was rinsed with 10% isopropanol in CHCl3. The eluent was concentrated and purified by preparative HPLC Normal phase, eluting with CH2Cl2/MeOH (0-30%). The 3rd peak was collected and concentrated to give 4-[5-(3-amino-5-methylphenyl)-4-chloro-1,3-thiazol-2-yl]-1,4-diazepan-2-one (45 mg, 0.134 mmol, 29.1% yield) as a brown solid.

Workup

  1. temperaturesubsequently cooled to room temperature
  2. filtrationThe dark mixture was filtered through a celite plug, which
  3. washwas rinsed with 10% isopropanol in CHCl3
  4. concentrationThe eluent was concentrated
  5. custompurified by preparative HPLC Normal phase
  6. washeluting with CH2Cl2/MeOH (0-30%)
  7. customThe 3rd peak was collected
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-1d1366f89c964d96869d8758ec68ee03
Source dataset
uspto-grants-2014_05
Patent number
US08735417B2

Reaction notes

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