Diisopropylethylamine → (S)-2-Amino-1-{4-[(4-benzyloxy-phenyl)-(3-methyl-but-2-enyl)-amino]-piperidin-1-yl}-4-methyl-pentan-1-one

HRID 2299891Notes

Reaction equation

HRID 2299891 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([N:15]([CH2:22][CH:23]=[C:24]([CH3:26])[CH3:25])[CH:16]2[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.O.C([NH:44][C@H:45]([C:50](O)=[O:51])[CH2:46][CH:47]([CH3:49])[CH3:48])(OC(C)(C)C)=O.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CCOC(C)=O.CN(C=O)C>[NH2:44][C@@H:45]([CH2:46][CH:47]([CH3:49])[CH3:48])[C:50]([N:19]1[CH2:20][CH2:21][CH:16]([N:15]([C:12]2[CH:13]=[CH:14][C:9]([O:8][CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)=[CH:10][CH:11]=2)[CH2:22][CH:23]=[C:24]([CH3:26])[CH3:25])[CH2:17][CH2:18]1)=[O:51]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10641624(4-Benzyloxy-phenyl)-(3-methyl-but-2-enyl)-piperidin-4-yl-amineHCID 12373896N-Boc-L-Leucine Hydrate

Product 1

HCID 10004622(S)-2-Amino-1-{4-[(4-benzyloxy-phenyl)-(3-methyl-but-2-enyl)-amino]-piperidin-1-yl}-4-methyl-pentan-1-oneYield 85.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

(4-Benzyloxy-phenyl)-(3-methyl-but-2-enyl)-piperidin-4-yl-amine (Ic, 1.03 g, 2.94 mmol) was dissolved DMF (15 mL) and treated with Hunig's base (1.3 mL, 7.4 mmol), Boc-L-leucine hydrate (0.74 g, 2.94 mmol), and HBTU (1.11 g, 2.94 mmol). The reaction was stirred for 4.5 hours, then diluted with EtOAc (200 mL), washed with saturated bicarbonate solution and brine, dried over Na2SO4, and concentrated. The crude material was chromatographed on silica gel eluting with 5% (MeOH/CH2Cl2) to give 1.17 g (71%) of the desired product.

Workup

  1. washwashed with saturated bicarbonate solution and brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated
  4. customThe crude material was chromatographed on silica gel eluting with 5% (MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-d8faac34d3ed4866b23e20b238422345
Source dataset
uspto-grants-2002_12
Patent number
US06495715B2

Reaction notes

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