Imidazole → {5-Chloro-2-[(R)-4-(2-pyrazol-1-yl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-cyclopentyl-amine

HRID 336497Notes

Reaction equation

HRID 336497 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([NH:11][CH:12]3[CH2:16][CH2:15][CH2:14][CH2:13]3)[CH:10]=1)[NH:7][C:6]([C:17]1[S:18][CH2:19][C@@H:20]([CH2:22][CH2:23]O)[N:21]=1)=[CH:5]2.II.N1C=CN=C1.[NH:32]1[CH:36]=[CH:35][CH:34]=[N:33]1.[H-].[Na+]>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([NH:11][CH:12]3[CH2:16][CH2:15][CH2:14][CH2:13]3)[CH:10]=1)[NH:7][C:6]([C:17]1[S:18][CH2:19][C@@H:20]([CH2:22][CH2:23][N:32]3[CH:36]=[CH:35][CH:34]=[N:33]3)[N:21]=1)=[CH:5]2

Participants

7

Reactant 5

HCID 795ImidazoleHCID 807IodineHCID 1048PyrazoleHCID 24758Sodium hydrideHCID 251961462-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethanol

Product 1

HCID 59543102{5-Chloro-2-[(R)-4-(2-pyrazol-1-yl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-cyclopentyl-amineYield 52.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethanol (81 mg, 0.11 mmol) prepared in Example 5 was dissolved in tetrahydrofuran (4 mL). Iodine (13.2 mg, 0.11 mmol) and imidazole (9.7 mg, 0.14 mmol) were added thereto, and the mixture was stirred for 2 h at room temperature. After completion of the reaction, the reaction mixture was filtered to remove solid moiety. The solvent was removed under reduced pressure, and tetrahydrofuran (4 mL) was added to the residue. Pyrazole (58 mg, 0.85 mmol) and sodium hydride (60% mineral oil, 21 mg, 0.85 mmol) were added thereto, and the mixture was stirred for 8 h at room temperature. The reaction was quenched by water, and the reaction mixture was extracted with ethyl acetate, dried over anhydrous magnesium sulfate, and filtered. The solvent was removed under reduced pressure, and the residue was purified by column chromatography to give the title compound (24 mg, Yield 34%).

Workup

  1. customAfter completion of the reaction
  2. filtrationthe reaction mixture was filtered
  3. customto remove solid moiety
  4. customThe solvent was removed under reduced pressure, and tetrahydrofuran (4 mL)
  5. additionwas added to the residue
  6. stirringthe mixture was stirred for 8 h at room temperature
  7. customThe reaction was quenched by water
  8. extractionthe reaction mixture was extracted with ethyl acetate
  9. dry with materialdried over anhydrous magnesium sulfate
  10. filtrationfiltered
  11. customThe solvent was removed under reduced pressure
  12. customthe residue was purified by column chromatography

Sources & evidence

ORD record
ord-f4246a241c714cb7be3341d8e904f16b
Source dataset
uspto-grants-2014_11
Patent number
US08889691B2

Reaction notes

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