1,2-Dichloroethane → HCID 24877156, compound

HRID 887956Notes

Reaction equation

HRID 887956 reaction equation
[NH2:1][C@@H:2]([CH2:28][CH:29]([CH3:31])[CH3:30])[C:3]([N:5]1[CH2:10][CH2:9][CH2:8][CH:7]([N:11]([CH:25]2[CH2:27][CH2:26]2)[S:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=2)(=[O:14])=[O:13])[CH2:6]1)=[O:4].[BH-](O[C:42]([CH3:44])=O)(OC(C)=O)OC(C)=O.[Na+].Cl[CH2:47]CCl>>[CH:25]1([N:11]([CH:7]2[CH2:8][CH2:9][CH2:10][N:5]([C:3](=[O:4])[C@@H:2]([NH:1][CH:42]([CH3:44])[CH3:47])[CH2:28][CH:29]([CH3:31])[CH3:30])[CH2:6]2)[S:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:23])([F:24])[F:22])[CH:16]=2)(=[O:14])=[O:13])[CH2:26][CH2:27]1

Participants

4

Reactant 3

HCID 111,2-DichloroethaneHCID 5049666Sodium triacetoxyborohydrideHCID 24877035HCID 24877035, compound

Product 1

HCID 24877156HCID 24877156, compound

Procedure

(2S)N-Cyclopropyl-N-[1-(2-isopropylamino-4-methylpentanoyl)-piperidin-3-yl]-3-trifluoromethylbenzenesulfonamide (18) was prepared as follows. A solution of compound 8 prepared in Example 2 (100 mg, 0.22 mmol), compound 17 (12 mg, 0.22 mmol, Aldrich) and 4 Å molecular sieves (500 mg) in 2 mL of 1,2-dichloroethane was shaken at room temperature for 10 minutes, and then, NaB(OAc)3H (43 mg, 0.22 mmol) was charged. The resulting mixture was shaken at room temperature for 24 hours. The reaction mixture was quenched with MeOH (0.2 mL), water (2 mL) was added, and the mixture was extracted with DCM (3×4 mL). The organic layers were combined and then washed with brine, dried over Na2SO3, concentrated under vacuum and purified by column (silica gel, EtOAc, then EtOAc/MeOH 10/1) to give the title compound 18 as a free base, which was converted to its HCl-salt by treating with HCl (1 N aqueous) and drying under vacuum (white solid, 60 mg, yield 65%). 1H NMR (400 MHz, CD3OD): δ 8.10-8.22 (m, 2H), 8.06 (dd, j=7.7, 7.8 Hz, 1H), 7.91 (dd, j=7.8, 7.9 Hz, 1H), 4.45-4.55 (m, 2H), 3.75-3.95 (m, 2H), 3.35-3.45 (m, 1H), 3.3-3.35 (m, 1H), 2.9-2.95 (m, 0.5H), 2.55-2.64 (m, 0.5H), 1.35-2.15 (m, 14H), 0.75-1.20 (m, 10H); LC: 100%; MS: m/z=504 (M+1).

Workup

  1. custom(2S)N-Cyclopropyl-N-[1-(2-isopropylamino-4-methylpentanoyl)-piperidin-3-yl]-3-trifluoromethylbenzenesulfonamide (18) was prepared
  2. customThe reaction mixture was quenched with MeOH (0.2 mL), water (2 mL)
  3. additionwas added
  4. extractionthe mixture was extracted with DCM (3×4 mL)
  5. washwashed with brine
  6. dry with materialdried over Na2SO3
  7. concentrationconcentrated under vacuum
  8. custompurified by column (silica gel, EtOAc

Sources & evidence

ORD record
ord-52c08ccbc09649acbeac74eb079eb102
Source dataset
uspto-grants-2012_08
Patent number
US08247442B2

Reaction notes

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