1-Methylimidazole → HCID 59428649, compound

HRID 504151Notes

Reaction equation

HRID 504151 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([S:8]([N:11]2[CH2:16][CH2:15][CH2:14][CH2:13][C@H:12]2[C:17]([NH:19][C@@H:20]([CH2:24][C:25]2[CH:30]=[CH:29][C:28]([O:31][CH:32]([CH3:34])[CH3:33])=[CH:27][CH:26]=2)[C:21]([OH:23])=O)=[O:18])(=[O:10])=[O:9])[CH:5]=[CH:6][CH:7]=1.[NH2:35][CH:36]1[CH2:41][C:40]([CH3:43])([CH3:42])[NH:39][C:38]([CH3:45])([CH3:44])[CH2:37]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CN1C=CN=C1.C(=O)(O)[O-].[Na+]>C1COCC1>[CH:32]([O:31][C:28]1[CH:27]=[CH:26][C:25]([CH2:24][C@H:20]([NH:19][C:17]([C@@H:12]2[CH2:13][CH2:14][CH2:15][CH2:16][N:11]2[S:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=2)(=[O:10])=[O:9])=[O:18])[C:21](=[O:23])[NH:35][CH:36]2[CH2:37][C:38]([CH3:45])([CH3:44])[NH:39][C:40]([CH3:43])([CH3:42])[CH2:41]2)=[CH:30][CH:29]=1)([CH3:33])[CH3:34]

Participants

7

Reactant 5

HCID 13901-MethylimidazoleHCID 375244-Amino-2,2,6,6-tetramethylpiperidineHCID 516892Sodium BicarbonateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 59428655HCID 59428655, compound

Product 1

HCID 59428649HCID 59428649, compoundYield 63.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(S)-2-{[(S)-1-(3-Fluoro-benzenesulfonyl)-piperidine-2-carbonyl]-amino}-3-(4-isopropoxy-phenyl)-propionic acid (60 mg, 0.12 mmol), 4-amino-2,2,6,6-tetramethylpiperidine (25 mg, 0.16 mmol), TBTU (51 mg, 1.60 mmol) and N-methyl imidazole (13 mL, 0.16 mmol) were mixed in anhydrous THF (2 mL). The mixture was stirred overnight at room temperature. A saturated aqueous sodium bicarbonate solution was added and the mixture was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The resulting oil was chromatographed (dichloromethane/methanol, 95/5) on silica gel to afford 48 mg (63%) of the title compound as a clear glass. MS: m/e 631.3 (M+H). 1H NMR (300 MHz, d6-DMSO): δ0.70-1.60 (m, 28H), 1.90 (d, 1H, J=12 Hz), 2.75 (m, 2H), 3.20 (m, 1H), 3.60 (d, 1H, J=12 Hz), 3.90 (m, 1H), 4.25 (dd, 1H, J1=9 Hz, J2=6 Hz), 4.50 (m, 2H), 6.80 (d, 2H, J=12 Hz), 7.10 (d, 2H, J=12 Hz), 7.45 (m, 4H), 7.65 (d, 1H, J=12 Hz), 7.90 (d, 1H, J=12 Hz).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. dry with materialThe organic layer was dried over magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe resulting oil was chromatographed (dichloromethane/methanol, 95/5) on silica gel

Sources & evidence

ORD record
ord-ddc2382780724ed5880051e1b15d1599
Source dataset
uspto-grants-2010_08
Patent number
US07777042B2

Reaction notes

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