Acetic Acid → Tert-butyl (2-chloro-5-cyano-3-(3-(4-methylpiperazin-1-yl)propyl)phenyl)carbamate

HRID 921858Notes

Reaction equation

HRID 921858 reaction equation
[Cl:1][C:2]1[C:7]([CH2:8][CH2:9][CH:10]=O)=[CH:6][C:5]([C:12]#[N:13])=[CH:4][C:3]=1[NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18].[CH3:22][N:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1>[Cl:1][C:2]1[C:7]([CH2:8][CH2:9][CH2:10][N:26]2[CH2:27][CH2:28][N:23]([CH3:22])[CH2:24][CH2:25]2)=[CH:6][C:5]([C:12]#[N:13])=[CH:4][C:3]=1[NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 531671-MethylpiperazineHCID 5049666Sodium triacetoxyborohydrideHCID 131734942Tert-butyl (2-chloro-5-cyano-3-(3-oxopropyl)phenyl)carbamate

Product 1

HCID 131734943Tert-butyl (2-chloro-5-cyano-3-(3-(4-methylpiperazin-1-yl)propyl)phenyl)carbamateYield 83.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Tert-butyl (2-chloro-5-cyano-3-(3-oxopropyl)phenyl)carbamate (113 mg, 0.366 mmol) was taken up in THF (2 mL) and 1-methylpiperazine (0.081 mL, 0.732 mmol) and acetic acid (0.042 mL, 0.732 mmol) were added. The reaction was stirred for 10 min, and then sodium triacetoxyborohydride (233 mg, 1.098 mmol) was added. The reaction was stirred at room temperature for 1 h. The reaction mixture was quenched with saturated NaHCO3 and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated. The material was purified by flash column chromatography (0-10% MeOHIDCM; 24 g column). Tert-butyl (2-chloro-5-cyano-3-(3-(4-methylpiperazin-1-yl)propyl)phenyl)carbamate (120 mg) was obtained as a colorless oil.

Workup

  1. stirringThe reaction was stirred at room temperature for 1 h
  2. customThe reaction mixture was quenched with saturated NaHCO3
  3. extractionextracted with EtOAc
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe material was purified by flash column chromatography (0-10% MeOHIDCM; 24 g column)

Sources & evidence

ORD record
ord-0bb740036773425aafa90e17737b4910
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

Loading…