Triethylamine → 2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethanol

HRID 1045873Notes

Reaction equation

HRID 1045873 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][C:23](O)=[O:24])[N:21]=1)=[CH:5]2.C(N(CC)CC)C.C(Cl)(=O)C(C)C.[BH4-].[Na+]>C(Cl)Cl>[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][OH:24])[N:21]=1)=[CH:5]2

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 62325Isobutyryl chlorideHCID 4311764Sodium borohydrideHCID 25196145[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]acetic acid

Product 1

HCID 251961462-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethanolYield 74.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid (391 mg, 1 mmol) prepared in Example 4 was dissolved in DCM (10 mL). Triethylamine (280 ul, 2 mmol) and isobutyric acid chloride (106 mg, 1 mmol) were added thereto, and the mixture was stirred for 30 min at 0° C. After completion of the reaction, the solvent was removed under reduced pressure. The residue was diluted with THF. NaBH4 (74 mg, 2 mmol) was added thereto, and the mixture was stirred for 12 h. The reaction was quenched with a small amount of water. Again, excess water was added to the reaction mixture, which was then stirred for 30 min, extracted with EtOAc, dried over MgSO4, and filtered. The solvent was removed under reduced pressure, and the residue was purified by column chromatography to give the title compound (272 mg, Yield 72%).

Workup

  1. customAfter completion of the reaction
  2. customthe solvent was removed under reduced pressure
  3. additionThe residue was diluted with THF
  4. stirringthe mixture was stirred for 12 h
  5. customThe reaction was quenched with a small amount of water
  6. additionAgain, excess water was added to the reaction mixture, which
  7. stirringwas then stirred for 30 min
  8. extractionextracted with EtOAc
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. customThe solvent was removed under reduced pressure
  12. customthe residue was purified by column chromatography

Sources & evidence

ORD record
ord-c9eb311d25734d329645269190e981e5
Source dataset
uspto-grants-2013_10
Patent number
US08569307B2

Reaction notes

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