Triethylamine → HCID 68873849, compound

HRID 1927590Notes

Reaction equation

HRID 1927590 reaction equation
[CH2:1]([CH:3]([CH2:20][CH3:21])[C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([N:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)=[C:9]([F:19])[CH:8]=1)=[O:5])[CH3:2].[C:22]([O:26][C:27](N1CCN(C2C=CC(N)=CC=2F)CC1)=[O:28])([CH3:25])([CH3:24])[CH3:23].CCN(CC)CC>C(Cl)Cl>[C:22]([O:26][C:27]([N:16]1[CH2:15][CH2:14][N:13]([C:10]2[CH:11]=[CH:12][C:7]([NH:6][C:4](=[O:5])[CH:3]([CH2:1][CH3:2])[CH2:20][CH3:21])=[CH:8][C:9]=2[F:19])[CH2:18][CH2:17]1)=[O:28])([CH3:25])([CH3:24])[CH3:23]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 162036301,1-Dimethylethyl 4-(4-amino-2-fluorophenyl)-1-piperazinecarboxylateHCID 58870794HCID 58870794, compound

Product 1

HCID 68873849HCID 68873849, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-Ethyl-N-(3-fluoro-4-piperazin-1-yl-phenyl)-butyramide. To a solution of 4-(4-amino-2-fluoro-phenyl)-piperazine-1-carboxylic acid tert-butyl ester (2.0 g, 8.9 mmol) and Et3N (1.4 mL, 10.0 mmol) in DCM (60 mL) was added 1-ethylbutyryl chloride (1.4 mL, 10.0 mol). The mixture was stirred for 18 h, quenched with 1 N NaHCO3 (50 mL), and extracted with DCM (3×50 mL). The organic layers were combined, dried (Na2SO4), and concentrated. Chromatography of the residue (SiO2; EtOAc/hexanes) gave 4-[4-(2-ethyl-butyrylamino)-2-fluoro-phenyl]-piperazine-1-carboxylic acid tert-butyl ester. A mixture of this intermediate in MeOH (25 mL) and 2 N HCl in Et2O (10 mL) was stirred for 18 h. The solution was concentrated to give 2-ethyl-N-(3-fluoro-4-piperazin-1-yl-phenyl)-butyramide hydrochloride. This salt was treated with 1 N NaOH (10 mL) and extracted with EtOAc (40 mL). The organic layer was dried and concentrated to give the title compound as the free base (1.5 g, 58%). MS (ESI): mass calcd. for C16H24FN3O, 293.19. m/z found, 294.4 [M+H]+. 1H NMR (CDCl3): 7.25-7.23 (m, 1H), 7.17 (s, 1H), 6.58-6.55 (m, 1H), 3.08-3.00 (m, 8H), 2.02-1.99 (m, 1H), 1.80-1.50 (m, 4H), 1.00-0.95 (m, 6H).

Workup

  1. customquenched with 1 N NaHCO3 (50 mL)
  2. extractionextracted with DCM (3×50 mL)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-84ff63e0792e4ab387556514cf70a6b1
Source dataset
uspto-grants-2012_05
Patent number
US08183239B2

Reaction notes

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