2-Aminothiazole → HCID 59200360, compound

HRID 1685290Notes

Reaction equation

HRID 1685290 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[CH:5][N:6]=1.Cl[C:8]1[N:13]=[CH:12][C:11]([CH2:14][N:15]([CH3:23])[C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[CH:10][CH:9]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[CH3:23][N:15]([CH2:14][C:11]1[CH:12]=[N:13][C:8]([NH:1][C:2]2[S:3][CH:4]=[CH:5][N:6]=2)=[CH:9][CH:10]=1)[C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:19])[CH3:20]

Participants

7

Reactant 3

HCID 21552-AminothiazoleHCID 10340Sodium CarbonateHCID 59200379HCID 59200379, compound

Product 1

HCID 59200360HCID 59200360, compoundYield 60.4%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)Catalyst2×HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
130 °C

Procedure

A suspension of 2-aminothiazole (0.556 g, 5.55 mmol, 1.15 eq), tert-butyl (6-chloropyridin-3-yl)methyl(methyl)carbamate (1.24 g, 4.83 mmol), sodium carbonate (0.717 g, 6.76 mol, 1.4 eq) and XANTPHOS (0.034 g, 0.058 mmol, 0.012 eq) in THF (12 mL, bubbled with argon for 5 minutes) was bubbled again with argon for 5 additional minutes. Tris(dibenzylideneacetone)dipalladium (0) (0.018 g, 0.019 mmol, 0.004 eq) was then added to the suspension which was heated at 130° C. for 18 hours. Tris(dibenzylideneacetone)dipalladium (0) (0.018 g, 0.019 mmol, 0.004 eq) and XANTPHOS (0.034 g, 0.058 mmol, 0.012 eq) were added again and the reaction was stirred for 18 more hours. The same was repeated a second time. The mixture was cooled down to RT and filtered. The THF filtrate was evaporated and the residue (1.72 g) was purified on Biotage silica gel chromatography (hexane/ethyl acetate 1:1 to 0:1) to give the title material (0.934 g, 60%). 1H NMR (400 MHz, CDCl3) δ ppm: 1.52 (9H, s), 2.84 (3H, s), 4.40 (2H, s), 6.86 (1H, d, J=3.54 Hz), 6.92 (1H, d, J=8.59 Hz), 7.44 (1H, d, J=3.79 Hz), 7.57 (1H, d, J=19.45 Hz) 8.27 (1H, s).

Workup

  1. customwas bubbled again with argon for 5 additional minutes
  2. temperatureThe mixture was cooled down to RT
  3. filtrationfiltered
  4. customThe THF filtrate was evaporated
  5. customthe residue (1.72 g) was purified on Biotage silica gel chromatography (hexane/ethyl acetate 1:1 to 0:1)

Sources & evidence

ORD record
ord-0a8b65ff3c2b436891933f6eaac5b953
Source dataset
uspto-grants-2012_04
Patent number
US08148400B2

Reaction notes

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