Triethylamine → 4-({Ethyl-[7-(4-methanesulfonyl-benzoylamino)-1,2,3,4-tetrahydro-naphthalen-2-yl]-amino}-methyl)-piperidine-1-carboxylic acid isopropylamide

HRID 983459Notes

Reaction equation

HRID 983459 reaction equation
[CH2:1]([N:3]([CH2:27][CH:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1)[CH:4]1[CH2:13][C:12]2[CH:11]=[C:10]([NH:14][C:15](=[O:26])[C:16]3[CH:21]=[CH:20][C:19]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:18][CH:17]=3)[CH:9]=[CH:8][C:7]=2[CH2:6][CH2:5]1)[CH3:2].C(N(CC)CC)C.[CH:41]([N:44]=[C:45]=[O:46])([CH3:43])[CH3:42]>C(Cl)Cl>[CH:41]([NH:44][C:45]([N:31]1[CH2:30][CH2:29][CH:28]([CH2:27][N:3]([CH2:1][CH3:2])[CH:4]2[CH2:5][CH2:6][C:7]3[C:12](=[CH:11][C:10]([NH:14][C:15](=[O:26])[C:16]4[CH:21]=[CH:20][C:19]([S:22]([CH3:25])(=[O:23])=[O:24])=[CH:18][CH:17]=4)=[CH:9][CH:8]=3)[CH2:13]2)[CH2:33][CH2:32]1)=[O:46])([CH3:43])[CH3:42]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 61277Isopropyl isocyanateHCID 11248400N-[7-(ethyl-piperidin-4-ylmethyl-amino)-5,6,7,8-tetrahydro-naphthalen-2-yl]-4-methanesulfonyl-benzamide

Product 1

HCID 113074364-({Ethyl-[7-(4-methanesulfonyl-benzoylamino)-1,2,3,4-tetrahydro-naphthalen-2-yl]-amino}-methyl)-piperidine-1-carboxylic acid isopropylamideYield 86.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To an ice-cold solution of N-[7-(ethyl-piperidin-4-ylmethyl-amino)-5,6,7,8-tetrahydro-naphthalen-2-yl]-4-methanesulfonyl-benzamide (1.3 g, 2.3 mmol) in methylene chloride (40 mL) under a nitrogen atmosphere was added the triethylamine (1.3 mL, 9.2 mmol, 4 eq.) in a single portion followed by the isopropylisocyanate (0.33 mL, 3.3 mmol, 1.4 eq). The reaction was allowed to warm to room temperature and stirred for 24 h. The reaction was concentrated in vacuo and partitioned between EtOAc (75 mL) and 10% aq. sodium hydroxide (40 mL). The aqueous layer was extracted with EtOAc (2×30 mL) and the combined EtOAc layers were dried over MgSO4, filtered, and concentrated. Trituration with ether afforded 4-({ethyl-[7-(4-methanesulfonyl-benzoylamino)-1,2,3,4-tetrahydro-naphthalen-2-yl]-amino}-methyl)-piperidine-1-carboxylic acid isopropylamide 1 as a light pink solid (1.1 g). [M+H]+=555.

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. custompartitioned between EtOAc (75 mL) and 10% aq. sodium hydroxide (40 mL)
  3. extractionThe aqueous layer was extracted with EtOAc (2×30 mL)
  4. dry with materialthe combined EtOAc layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-f4b0e2d23c6e47f5b6229ff207f2b141
Source dataset
uspto-grants-2005_03
Patent number
US06864266B2

Reaction notes

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