1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 57874393, compound

HRID 1093797Notes

Reaction equation

HRID 1093797 reaction equation
CCN(C(C)C)C(C)C.[CH3:10][N:11]([CH3:27])[C:12]1[CH:13]=[C:14]([C:18]2[CH:23]=[CH:22][C:21]([C:24]([OH:26])=O)=[CH:20][CH:19]=2)[CH:15]=[CH:16][CH:17]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[NH2:50][CH2:51][C:52]([N:54]1[CH2:59][CH2:58][CH:57]([O:60][C:61]2[CH:66]=[CH:65][CH:64]=[CH:63][C:62]=2[Cl:67])[CH2:56][CH2:55]1)=[O:53]>CN(C=O)C.O>[Cl:67][C:62]1[CH:63]=[CH:64][CH:65]=[CH:66][C:61]=1[O:60][CH:57]1[CH2:56][CH2:55][N:54]([C:52](=[O:53])[CH2:51][NH:50][C:24]([C:21]2[CH:20]=[CH:19][C:18]([C:14]3[CH:15]=[CH:16][CH:17]=[C:12]([N:11]([CH3:10])[CH3:27])[CH:13]=3)=[CH:23][CH:22]=2)=[O:26])[CH2:59][CH2:58]1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 10610132HCID 10610132, compoundHCID 665915282-Amino-1-[4-(2-chloro-phenoxy)-piperidin-1-yl]-ethanone hydrochloride

Product 1

HCID 57874393HCID 57874393, compoundYield 22.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (170 mg, 1.3 mmol) was added to a stirred solution of to a stirred solution of 3′-dimethylamino-biphenyl-4-carboxylic acid (80 mg, 0.33 mmol) (generated from methyl 3′-amino(1,1′-biphenyl)-4-carboxylate) in DMF (2 mL) followed by HOBt (49 mg, 0.36 mmol) and EDCI (126 mg, 0.66 mmol). After 2 minutes of stirring, 2-amino-1-[4-(2-chloro-phenoxy)-piperidin-1-yl]-ethanone hydrochloride (110 mg, 0.36 mmol) (prepared according to Step 1 and 5 of the General Scheme) was added and the resulting mixture was stirred at room temperature overnight. Cold water was then added and the product was extracted with EtOAc and the organic layer was washed with brine. The organic phase was dried over Na2SO4 and concentrated under reduced pressure The residue was purified by preparative HPLC to afford 36 mg (22% Yield) of 3′-dimethylamino-biphenyl-4-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 492, 86.69%. 1H NMR (300 MHz, DMSO-d6): δ 8.6 (t, 1H), 8.0-7.9 (d, 2H), 7.8-7.7 (d, 3H), 7.5-7.4 (d, 1H), 7.36-7.24 (m, 3H), 7.1-7.0 (m, 2H), 7.0-6.94 (m, 1H), 6.88-6.8 (d, 1H), 4.8 (q, 1H), 4.2 (d, 2H), 4.0-3.7 (m, 4H), 3.5 (m, 3H), 3.0 (s, 6H), 2.0-1.8 (m, 3H), 1.8-1.6 (m, 3H).

Workup

  1. additionwas added
  2. stirringthe resulting mixture was stirred at room temperature overnight
  3. extractionthe product was extracted with EtOAc
  4. washthe organic layer was washed with brine
  5. dry with materialThe organic phase was dried over Na2SO4
  6. concentrationconcentrated under reduced pressure The residue
  7. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-43cc842d8e0345c4b9b80621ebb65987
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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