Potassium Carbonate → 4'-Fluoro-biphenyl-4-carboxylic acid (6-piperidin-1-ylmethyl-1,2,3,4-tetrahydro-naphthalen-2-yl)-amide

HRID 968654

Reaction equation

HRID 968654 reaction equation
[NH2:1][CH2:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH2:9][CH:8]([NH:13][C:14]([C:16]1[CH:21]=[CH:20][C:19]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)=[CH:18][CH:17]=1)=[O:15])[CH2:7][CH2:6]2.Br[C:30](Br)([CH2:33][CH3:34])[CH2:31][CH3:32].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[N:1]1([CH2:2][C:3]2[CH:4]=[C:5]3[C:10](=[CH:11][CH:12]=2)[CH2:9][CH:8]([NH:13][C:14]([C:16]2[CH:21]=[CH:20][C:19]([C:22]4[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=4)=[CH:18][CH:17]=2)=[O:15])[CH2:7][CH2:6]3)[CH2:34][CH2:33][CH2:30][CH2:31][CH2:32]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 113947174'-Fluoro-biphenyl-4-carboxylic acid (6-aminomethyl-1,2,3,4-tetrahydro-naphthalen-2-yl)-amideHCID 135557303,3-Dibromopentane

Product 1

HCID 112245284'-Fluoro-biphenyl-4-carboxylic acid (6-piperidin-1-ylmethyl-1,2,3,4-tetrahydro-naphthalen-2-yl)-amideYield 57%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 4′-fluoro-biphenyl-4-carboxylic acid (6-aminomethyl-1,2,3,4-tetrahydro-naphthalen-2-yl)-amide, 4, (0.054 g, 0.14), dibromopentane (0.022 mL, 0.16 mmol) and K2CO3 (0.099 g, 0.72 mmol) in DMF (2 mL) is stirred at room temperature for 18 hours. The reaction solution is filtered and the filtrate concentrated in vacuo to leave a crude residue which is purified by reversed prep-HPLC using CH3CN—H2O (0.1% TFA) to afforded 36 mg (57% yield) of the desired product as a foaming solid. 1H NMR (300 MHz, CD3OD) δ 7.94 (d, J=8.4 Hz, 2H), 7.72 (m, 4H), 7.25 (t, J=9.6 Hz, 5H), 4.33 (m, 1H), 4.24 (s, 2H), 3.44-3.56 (m, 3H), 3.16-3.24 (br, 1H), 2.84-3.07 (m, 4H), 2.20-2.35 (br, 1H), 1.67-2.02 (m, 6H), 1.54 (m, H1); 13C NMR (75 MHz, CD3OD) δ 168.4, 164.8, 143.4, 137.4, 137.0, 130.9, 131.5, 130.0, 128.9, 128.8, 128.5, 127.9, 126.8, 115.8, 115.5, 60.5, 52.7, 46.6, 35.0, 28.9, 28.3, 22.9, 21.6; 19F NMR (282 MHz, CD3OD) δ 46.3; LRMS: 443.6 (M+H); HRMS: calcd for C29H32FN2O: 443.2499 (M+H), found: 443.2506.

Workup

  1. filtrationThe reaction solution is filtered
  2. concentrationthe filtrate concentrated in vacuo
  3. customto leave a crude residue which
  4. customis purified by reversed

Sources & evidence

ORD record
ord-6f1b5f7ab23149a7abdb256e821d2de9
Source dataset
uspto-grants-2007_12
Patent number
US07304065B2

Linked notes

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