2-Aminothiazole → (6-(Thiazol-2-ylamino)pyridine-3-yl)methanol

HRID 1685286Notes

Reaction equation

HRID 1685286 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([CH2:8][OH:9])=[CH:4][CH:3]=1.[NH2:10][C:11]1[S:12][CH:13]=[CH:14][N:15]=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>[S:12]1[CH:13]=[CH:14][N:15]=[C:11]1[NH:10][C:2]1[N:7]=[CH:6][C:5]([CH2:8][OH:9])=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 21552-AminothiazoleHCID 10340Sodium CarbonateHCID 177161(6-Chloropyridin-3-yl)methanol

Product 1

HCID 59200466(6-(Thiazol-2-ylamino)pyridine-3-yl)methanolYield 93%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
120 °C

Procedure

A suspension of (6-chloropyridin-3-yl)methanol (11.23 g, 78.22 mmol), 2-aminothiazole (9.40 g, 93.86 mmol, 1.2 eq), sodium carbonate (11.6 g, 109.5 mol, 1.4 eq) and XANTPHOS (0.543 g, 0.939 mmol, 0.012 eq) in THF (60 mL, bubbled with argon for 5 minutes) was bubbled again with argon for 5 additional minutes. Tris(dibenzylideneacetone)dipalladium (0) (0.269 g, 0.293 mmol, 0.004 eq) was then added to the suspension which was heated at 120° C. for 4 days. The mixture was cooled down to RT and filtered. The resulting solid was washed with toluene and tetrahydrofuran and suspended in water. This suspension was stirred for ˜0.5 hour and then filtered. The resulting solid was dried overnight under vacuum to give the title material (15.072 g, 93%) as a solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 4.44 (2H, d, J=5.6 Hz), 5.16 (1H, t, J=5.6 Hz), 6.98 (1H, d, J=3.7 Hz), 7.04 (1H, d, J=8.5 Hz), 7.37 (1H, d, J=3.6 Hz), 7.66 (1H, dd, J=8.5 and 2.2 Hz), 8.21 (1H, br d, J=1.5 Hz), 11.22 (1H, s). LC/MS (M+H)+: 208. HPLC ret. time (Condition A): 0.375 min.

Workup

  1. customwas bubbled again with argon for 5 additional minutes
  2. temperatureThe mixture was cooled down to RT
  3. filtrationfiltered
  4. washThe resulting solid was washed with toluene and tetrahydrofuran
  5. filtrationfiltered
  6. customThe resulting solid was dried overnight under vacuum

Sources & evidence

ORD record
ord-e335b1c74b6a42168c7d96bbb9454553
Source dataset
uspto-grants-2012_04
Patent number
US08148400B2

Reaction notes

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