Triethylamine → HCID 24877035, compound

HRID 887955Notes

Reaction equation

HRID 887955 reaction equation
Cl.[CH:2]1([N:5]([CH:19]2[CH2:24][CH2:23][CH2:22][NH:21][CH2:20]2)[S:6]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=2)(=[O:8])=[O:7])[CH2:4][CH2:3]1.C([N:27]([CH2:30][CH3:31])CC)C.ON1[C:37]2C=CC=[CH:41][C:36]=2N=N1.N(C(OC(C)C)=O)=N[C:44](OC(C)C)=[O:45]>ClCCl>[NH2:27][C@@H:30]([CH2:31][CH:36]([CH3:41])[CH3:37])[C:44]([N:21]1[CH2:22][CH2:23][CH2:24][CH:19]([N:5]([CH:2]2[CH2:4][CH2:3]2)[S:6]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:16])[F:17])[CH:10]=2)(=[O:7])=[O:8])[CH2:20]1)=[O:45]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 757711-HydroxybenzotriazoleHCID 68982941HCID 68982941, compound

Product 1

HCID 24877035HCID 24877035, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(2S)N-[1-(2-Amino-4-methylpentanoyl)-piperidin-3-yl]-N-cyclo-propyl-3-trifluoromethylbenzenesulfonamide (8) was prepared as follows. A solution of compound 6 (see Example 1) (300 mg, 0.78 mmol), triethylamine (TEA, 0.5 mL), 1-hydroxybenzotriazole (HOBT) (100 mg), compound 2 (0.2 g, 0.86 mmol, Adv. Chem. Tech.), and dichloromethane (DCM, 4 mL) was cooled with ice-water and treated with diisopropyl azodicarboxylate (DIC) (0.14 mL, 0.88 mmol). The resulting mixture was warmed to room temperature over 24 hours. The reaction mixture was cooled to 0° C. and the solid was removed by filtration. The liquid was concentrated and purified by column (silica) eluting with EtOAc/hexanes (1/1) to afford the BOC-protected product, which was dissolved in 1,4-dioxane (4 mL) and treated with HCl (4N in 1,4-dioxane 1 mL) at room temperature for 4 hours. The solvent was removed under vacuum and the residue was washed with Et2O (3×2 mL) to give the title compound 8 as a HCl-salt (white solid, 300 mg, yield 79%). 1H NMR (400 MHz, CD3OD): δ 7.90-8.28 (m, 4H, Ar—H), 4.15-4.55 (m, 2H), 3.75-3.95 (m, 2H), 3.35-3.45 (m, 0.5H), 3.05-3.15 (m, 0.5H), 2.85-2.95 (m, 0.5H), 2.55-2.65 (m, 0.5H), 1.45-2.15 (m, 8H), 0.75-1.15 (m, 10H). LC: 100%; MS: m/z=462 (M+1).

Workup

  1. temperatureThe reaction mixture was cooled to 0° C.
  2. customthe solid was removed by filtration
  3. concentrationThe liquid was concentrated
  4. custompurified by column (silica)
  5. washeluting with EtOAc/hexanes (1/1)

Sources & evidence

ORD record
ord-b1f49661f4b14e479cb6718a98d312f5
Source dataset
uspto-grants-2012_08
Patent number
US08247442B2

Reaction notes

Loading…