Triethylamine → HCID 58486395, compound

HRID 1890767Notes

Reaction equation

HRID 1890767 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[N:12][C:11]([N:14]3[CH2:19][CH2:18][CH:17]([NH:20][CH3:21])[CH2:16][CH2:15]3)=[C:10]([CH3:22])[C:9]=2[CH3:23])=[CH:4][CH:3]=1.[C:24]([O:28][C:29]([N:31]1[CH2:36][CH2:35][CH2:34][CH2:33][C@H:32]1[C:37]([OH:39])=O)=[O:30])([CH3:27])([CH3:26])[CH3:25].C(N(CC)CC)C.CCN=C=NCCCN(C)C.C([O-])(O)=O.[Na+]>C(Cl)Cl.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[N:12][C:11]([N:14]3[CH2:19][CH2:18][CH:17]([N:20]([CH3:21])[C:37]([C@@H:32]4[CH2:33][CH2:34][CH2:35][CH2:36][N:31]4[C:29]([O:28][C:24]([CH3:25])([CH3:26])[CH3:27])=[O:30])=[O:39])[CH2:16][CH2:15]3)=[C:10]([CH3:22])[C:9]=2[CH3:23])=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 516892Sodium BicarbonateHCID 688617(2S)-1-((tert-butoxy)carbonyl)piperidine-2-carboxylic acidHCID 67368812HCID 67368812, compound

Product 1

HCID 58486395HCID 58486395, compoundYield 49.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Sequentially treat a solution of 1-(6-(4-fluorophenyl)-4,5-dimethylpyridazin-3-yl)-N-methylpiperidin-4-amine (100 mg, 0.318 mmol) in CH2Cl2 (3.2 mL) with (S)-1-(tert-butoxycarbonyl)piperidine-2-carboxylic acid (109 mg, 0.477 mmol), triethylamine (0.067 mL, 0.477 mmol) and EDCI (92 mg, 0.477 mmol). Stir the resulting mixture at ambient temperature for 2 d. Pour the reaction mixture into H2O containing NaHCO3. Separate the layers, and extract the aqueous layer with CH2Cl2. Combine the organic layers, dry over Na2SO4, filter, and concentrate under reduced pressure. Purify the residue by flash silica gel chromatography (gradient of 0 to 2% 2 M NH3/MeOH in CH2Cl2) to afford the title compound as a white solid (82 mg, 49%). ES/MS m/z 526.2 (M+1).

Workup

  1. customSeparate the layers
  2. extractionextract the aqueous layer with CH2Cl2
  3. dry with materialdry over Na2SO4
  4. filtrationfilter
  5. concentrationconcentrate under reduced pressure
  6. customPurify the residue by flash silica gel chromatography (gradient of 0 to 2% 2 M NH3/MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-90db35d0fbf4484c89563afc9e6d2c4d
Source dataset
uspto-grants-2013_08
Patent number
US08507490B2

Reaction notes

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