Piperidine → HCID 69529729, compound

HRID 1814423Notes

Reaction equation

HRID 1814423 reaction equation
[C:1]([O:5][C:6]([C@@H:8]([NH:28]C(OCC1C2C=CC=CC=2C2C1=CC=CC=2)=O)[CH2:9][CH2:10][N:11]([CH:18]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH2:21][CH2:20][CH2:19]1)[CH2:12][CH2:13][CH2:14][C:15]([OH:17])=[O:16])=[O:7])([CH3:4])([CH3:3])[CH3:2].N1CCCCC1.[Br:52][C:53]1[CH:58]=[CH:57][C:56]([N:59]=[C:60]=[O:61])=[CH:55][CH:54]=1.CO.C(Cl)(Cl)Cl>CN(C=O)C>[Br:52][C:53]1[CH:58]=[CH:57][C:56]([NH:59][C:60](=[O:61])[NH:28][C@H:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][CH2:10][N:11]([CH:18]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[CH2:21][CH2:20][CH2:19]2)[CH2:12][CH2:13][CH2:14][C:15]([OH:17])=[O:16])=[CH:55][CH:54]=1

Participants

6

Reactant 4

HCID 8082PiperidineHCID 756094-Bromophenyl isocyanateHCID 21584188Chloroform methanolHCID 69746391HCID 69746391, compound

Product 1

HCID 69529729HCID 69529729, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-[[(3S)-3-(tert-butoxycarbonyl)-3-[[(9H-9-fluorenylmethoxy)carbonyl]amino]propyl](1,2,3,4-tetrahydro-1-naphthyl)amino]butanoic acid (18 mg, 0.029 mmol) in DMF (0.4 ml) was added piperidine (0.1 ml), and the mixture was stirred at RT for 1.5 h. The reaction mixture was concentrated under vacuum to dryness, and the residue was dissolved in CH2Cl2 (0.5 ml). To the solution was added 4-bromophenyl isocyanate (8.7 mg, 0.044 mmol), and the mixture was stirred at RT for 2h. The reaction mixture was adsorbed on a plate of silica gel and then developed with 10% methanol/chloroform to afford 2 diastereoisomers of 4-[[(3S)-3-(4-bromophenylureido)-3-(tert-butoxycarbonyl)propyl](1,2,3,4-tetrahydro-1-naphthyl)amino]butanoic acid (6.8 mg, 39%, less polar isomer, Compound 165): MS(ES+) m/e 588 [M+H]+; 1H NMR (400 MHz, CDCl3) δ 9.86 (br, 1H), 8.38 (br, 1H), 7.99 (br, 1H), 7.70 (d, J=7.8 Hz, 1H), 7.42 (d, 1=8.3 Hz, 2H), 7.25 (d, J=8.8 Hz, 2H), 7.08 (m, 3H), 4.81 (t, J=7.3 Hz, 1H), 4.41 (m, 1H), 3.42 (m, 1H), 2.97 (m, 1H), 2.71 (m, 1H), 2.59 (m, 1H), 2.46 (dd, J=16.3, 7.1 Hz, 1H), 2.18 (m, 2H), 1.95-1.74 (m, 4H), 1.62 (m, 1H), 1.48 (m, 1H), 1.32 (s, 9H). (7.4 mg, 43%, more polar isomer, Compound 166): MS(ES+) m/e 588 [M+H]+; 1H NMR (400 MHz, CDCl3) δ 9.16 (br, 1H), 8.57 (br, 1H), 7.58 (d, J=8.8 Hz, 1H), 7.42 (br, 1H), 7.33 (d, 1=8.8 Hz, 2H), 7.23 (d, J=8.8 Hz, 2H), 7.15 (m, 2H), 7.07 (m, 1H), 4.57 (t, J=7.3 Hz, 1H), 4.26 (m, 1H), 3.25 (m, 1H), 2.92 (m, 1H), 2.69 (m, 5H), 2.40 (m, 1H), 2.11 (m, 4H), 1.90 (m, 2H), 1.65 (m, 2H), 1.33 (s, 9H).

Workup

  1. concentrationThe reaction mixture was concentrated under vacuum to dryness
  2. dissolutionthe residue was dissolved in CH2Cl2 (0.5 ml)
  3. stirringthe mixture was stirred at RT for 2h

Sources & evidence

ORD record
ord-0482fade8e8e4b7dbf024a15a572495a
Source dataset
uspto-grants-2005_04
Patent number
US06875884B1

Reaction notes

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