2-Aminothiazole → HCID 58997071, compound

HRID 251150Notes

Reaction equation

HRID 251150 reaction equation
[C:1]([N:8]1[CH:12]=[CH:11][N:10]=[CH:9]1)([N:3]1[CH:7]=[CH:6]N=[CH:4]1)=[O:2].NC1[S:15]C=CN=1.CCN(C(C)C)C(C)C.[CH3:28][C:29]1[C:30]([CH2:35][N:36]([CH2:43][C:44]2[C:49]([CH3:50])=[CH:48][CH:47]=[CH:46][N:45]=2)[CH:37]2CCNC[CH2:38]2)=[N:31][CH:32]=[CH:33][CH:34]=1>C(Cl)Cl.CN(C=O)C>[S:15]1[CH:12]=[CH:11][N:10]=[C:9]1[NH:8][C:1]([N:3]1[CH2:4][CH2:38][CH:37]([N:36]([CH2:43][C:44]2[C:49]([CH3:50])=[CH:48][CH:47]=[CH:46][N:45]=2)[CH2:35][C:30]2[C:29]([CH3:28])=[CH:34][CH:33]=[CH:32][N:31]=2)[CH2:6][CH2:7]1)=[O:2]

Participants

7

Reactant 4

HCID 21552-AminothiazoleHCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 58996965Bis-(3-methyl-pyridin-2-ylmethyl)-piperidin-4-yl-amine

Product 1

HCID 58997071HCID 58997071, compoundYield 13%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 1,1′-carbonyldiimidazole (79.6 mg, 0.491 mmol), 2-aminothiazole (48.2 mg, 0.481 mmol), and DIPEA (0.17 mL, 0.97 mmol) in CH2Cl2 (5 mL) and DMF (2 mL) was stirred at room temperature for 4 h. The mixture was concentrated to a minimum volume, diluted with DMF (3 mL), and COMPOUND 249 (150 mg, 0.482 mmol) was added and stirred at 60° C. for 20 hours. The solution was concentrated to dryness, treated with saturated aqueous NaHCO3 (30 mL) and H2O (10 mL), and extracted with CH2Cl2 (3×10 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated. Purification of the crude material by flash chromatography on silica gel (CH2Cl2/MeOH/NH4OH, 90:5:5) followed by radial chromatography on a 1 mm TLC grade silica gel plate (CH2Cl2/MeOH/NH4OH, 96:2:2) provided COMPOUND 289 (27 mg, 13%) as a white solid. 1H NMR (CDCl3) δ 1.57-1.82 (m, 4H), 1.97 (d, 2H, J=11.7 Hz), 2.08 (s, 6H), 2.64-2.84 (m, 3H), 3.81 (s, 4H), 4.20 (d, 2H, J=12.9 Hz), 6.85 (d, 1H, J=3.6 Hz), 7.09 (dd, 2H, J=7.2, 5.1 Hz), 7.31 (d, 1H, J=3.6 Hz), 7.37 (d, 2H, J=7.5 Hz), 8.34 (d, 2H, J=4.5 Hz), 9.47 (br s, 1H); 13C NMR (CDCl3) 18.37, 27.47, 44.83, 54.97, 57.59, 113.16, 122.87, 133.78, 137.00, 138.47, 146.35, 153.46, 157.43, 161.07; ES-MS m/z 459 (M+Na). Anal. Calcd. for C23H28N6OS.0.3H2O.0.2 CH2Cl2: C, 60.71; H, 6.37; N, 18.31. Found: C, 61.05; H, 6.61; N, 17.94.

Workup

  1. concentrationThe mixture was concentrated to a minimum volume
  2. additionwas added
  3. concentrationThe solution was concentrated to dryness
  4. additiontreated with saturated aqueous NaHCO3 (30 mL) and H2O (10 mL)
  5. extractionextracted with CH2Cl2 (3×10 mL)
  6. dry with materialThe combined organic extracts were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification of the crude material by flash chromatography on silica gel (CH2Cl2/MeOH/NH4OH, 90:5:5)

Sources & evidence

ORD record
ord-8b2817532680426ab1fc4913605711ce
Source dataset
uspto-grants-2011_01
Patent number
US07863293B2

Reaction notes

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