2-Aminothiazole → HCID 58996995, compound

HRID 251166Notes

Reaction equation

HRID 251166 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[CH:5][N:6]=1.[C:7](N1C=CN=C1)(N1C=CN=C1)=[O:8].[CH3:19][C:20]1[C:21]([CH2:27][N:28]([CH2:35][C:36]2[C:41]([CH:42]([CH3:44])[CH3:43])=[CH:40][CH:39]=[CH:38][N:37]=2)[CH:29]2[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]2)=[N:22][CH:23]=[C:24]([CH3:26])[CH:25]=1>C(Cl)Cl.CC#N>[S:3]1[CH:4]=[CH:5][N:6]=[C:2]1[NH:1][C:7]([N:32]1[CH2:33][CH2:34][CH:29]([N:28]([CH2:27][C:21]2[C:20]([CH3:19])=[CH:25][C:24]([CH3:26])=[CH:23][N:22]=2)[CH2:35][C:36]2[C:41]([CH:42]([CH3:44])[CH3:43])=[CH:40][CH:39]=[CH:38][N:37]=2)[CH2:30][CH2:31]1)=[O:8]

Participants

6

Reactant 3

HCID 21552-AminothiazoleHCID 682631,1'-CarbonyldiimidazoleHCID 58997074(3,5-Dimethyl-pyridin-2-ylmethyl)-(3-isopropyl-pyridin-2-ylmethyl)-piperidin-4-yl-amine

Product 1

HCID 58996995HCID 58996995, compoundYield 36.3%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-aminothiazole (48 mg, 0.45 mmol) in CH2Cl2 (5 mL) was added 1,1′-carbonyldiimidazole (90 mg, 0.55 mmol) and the reaction was stirred at room temperature for 4 h. The reaction mixture was concentrated and dried in vacuo. The tan residue was dissolved in a solution of the (3,5-dimethyl-pyridin-2-ylmethyl)-(3-isopropyl-pyridin-2-ylmethyl)-piperidine-4-yl-amine (80 mg, 0.23 mmol) in CH3CN (5 mL) and warmed to 60° C. After 2 h at 60° C., the mixture was cooled and diluted with CH2Cl2/saturated NaHCO3 (1:1, 60 mL). The aqueous layer was extracted with CH2Cl2 (2×20 mL). The combined organic layer was dried (MgSO4), filtered, and concentrated to afford a yellow oil. Purification by radial chromatography on silica gel (1 mm plate; using CH2Cl2/MeOH/NH4OH; 100:1:1→25:1:1) afforded the product as a yellow oil (40 mg, 19%). 1H NMR (CDCl3) δ 0.94 (d, 6H, J=6.0 Hz), 1.63 (br m, 2H), 1.96 (d, 2H, J=12.0 Hz), 2.16 (s, 3H), 2.28 (s, 3H), 2.74-2.82 (m, 4H), 3.77 (s, 2H), 3.83 (s, 2H), 4.17 (s, 1H), 4.21 (s, 1H), 6.86 (d, 1H, J=3.0 Hz), 7.11-7.17 (m, 1H), 7.26 (s, 1H), 7.33 (d, 1H, J=3.0 Hz), 7.51 (d, 1H, J=9.0 Hz), 8.19 (s, 1H), 8.33 (d, 1H, J=3.0 Hz), 9.16 (br s, 1H). 13C NMR (CDCl3) δ 18.30, 18.47, 23.61, 27.44, 27.50, 30.09, 44.86, 53.85, 54.30, 113.09, 122.38, 123.26, 132.39, 133.25, 133.96, 135.57, 136.72, 139.16, 144.45, 146.06, 146.63, 153.93, 154.34, 156.16, 162.92. ES-MS m/z 479 [M+H]+. Anal. Calcd. for C26H34N6—SO.0.7CH2Cl2.0.7CH3CN: C, 59.54; H, 6.67; N, 16.56; S, 5.66. Found: C, 59.40; H, 6.91; N, 16.49; S, 5.46.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customdried in vacuo
  3. temperaturewarmed to 60° C
  4. waitAfter 2 h at 60° C.
  5. temperaturethe mixture was cooled
  6. extractionThe aqueous layer was extracted with CH2Cl2 (2×20 mL)
  7. dry with materialThe combined organic layer was dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto afford a yellow oil
  11. customPurification by radial chromatography on silica gel (1 mm plate; using CH2Cl2/MeOH/NH4OH; 100:1:1→25:1:1)

Sources & evidence

ORD record
ord-587f5faa88c1430eb14c56c414142132
Source dataset
uspto-grants-2011_01
Patent number
US07863293B2

Reaction notes

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