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Diisopropylethylamine → N-[3-(4-Cyclohexylcarbamoyl-4-fluoro-piperidin-1-ylmethyl)-phenyl]-5-methyl-nicotinamide

HRID 1486747
Notes
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Reaction equation

HRID 1486747 reaction equation
[CH:1]([C:3]1[CH:4]=[C:5]([NH:9][C:10](=[O:18])[C:11]2[CH:16]=[C:15]([CH3:17])[CH:14]=[N:13][CH:12]=2)[CH:6]=[CH:7][CH:8]=1)=O.Cl.[CH:20]1([NH:26][C:27]([C:29]2([F:35])[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]2)=[O:28])[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1.CCN(C(C)C)C(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[CH:20]1([NH:26][C:27]([C:29]2([F:35])[CH2:34][CH2:33][N:32]([CH2:1][C:3]3[CH:4]=[C:5]([NH:9][C:10](=[O:18])[C:11]4[CH:16]=[C:15]([CH3:17])[CH:14]=[N:13][CH:12]=4)[CH:6]=[CH:7][CH:8]=3)[CH2:31][CH2:30]2)=[O:28])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 86706560N-(3-Formyl-phenyl)-5-methyl-nicotinamideHCID 867065644-Fluoro-piperidine-4-carboxylic acid cyclohexylamide hydrochloride

Product 1

HCID 86706563N-[3-(4-Cyclohexylcarbamoyl-4-fluoro-piperidin-1-ylmethyl)-phenyl]-5-methyl-nicotinamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of N-(3-formyl-phenyl)-5-methyl-nicotinamide L-1 (60 mg, 0.25 mmol) and 4-fluoro-piperidine-4-carboxylic acid cyclohexylamide hydrochloride (66 mg, 0.25 mmol) in DCM (3 mL) is treated with DIPEA (0.128 mL, 0.75 mmol). Sodium triacetoxyborohydride (132 mg, 0.62 mmol) is added at once and the mixture is stirred at RT for 18 h. The mixture is diluted with DCM (5 mL) and washed twice with aq. sat. NaHCO3 (5 mL). The organic phase is dried over MgSO4 and evaporated. The residue is dissolved in acetonitrile and purified by prep HPLC E, delivering the title compound as a colorless powder, LC-MS A: tR=0.62 min; [M+H]+=453.4. 1H-NMR (CDCl3): δ 1-1.4 (m, 5H), 1.6-1.8 (m, 6H), 1.9-2.1 (m, 2H), 2.2-2.4 (m, 4H), 3.45 (s, 3H), 2.7-2.8 (m, 2H), 3.7-3.8 (m, 1H), 6.28 (t, J=6.5, 1H), 7.15 (d, J=8, 1H), 7.35 (t, J=8, 1H), 7.55 (s, 1H), 7.73 (d, J=8, 1H), 8.05 (s, 1H), 8.12 (s, 1H), 8.61 (s, 1H), 8.93 (s, 1H).

Workup

  1. washwashed twice with aq. sat. NaHCO3 (5 mL)
  2. dry with materialThe organic phase is dried over MgSO4
  3. customevaporated
  4. dissolutionThe residue is dissolved in acetonitrile
  5. custompurified by prep HPLC E

Sources & evidence

ORD record
ord-0aa82bfad9424cf39de4c1fcc6bfd2fe
Source dataset
uspto-grants-2016_08
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09428456B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes