Diisopropylethylamine → 5-Pyridin-3-yl-thiophene-2-carboxylic acid 3-(2-methyl-1,2,3,4-tetrahydro-isoquinolin-7-ylcarbamoyl)-benzylamide

HRID 2367739Notes

Reaction equation

HRID 2367739 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[S:11][C:10]([C:12]([OH:14])=O)=[CH:9][CH:8]=2)[CH:2]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.Cl.Cl.[NH2:48][CH2:49][C:50]1[CH:51]=[C:52]([CH:67]=[CH:68][CH:69]=1)[C:53]([NH:55][C:56]1[CH:65]=[C:64]2[C:59]([CH2:60][CH2:61][N:62]([CH3:66])[CH2:63]2)=[CH:58][CH:57]=1)=[O:54]>CN(C=O)C>[CH3:66][N:62]1[CH2:61][CH2:60][C:59]2[C:64](=[CH:65][C:56]([NH:55][C:53]([C:52]3[CH:51]=[C:50]([CH:69]=[CH:68][CH:67]=3)[CH2:49][NH:48][C:12]([C:10]3[S:11][C:7]([C:3]4[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=4)=[CH:8][CH:9]=3)=[O:14])=[O:54])=[CH:57][CH:58]=2)[CH2:63]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 47391005-pyridin-3-ylthiophene-2-carboxylic AcidHCID 666490723-(2-Methyl-1,2,3,4-tetrahydro-isoquinolin-7-ylcarbamoyl)benzylamine dihydrochloride

Product 1

HCID 566017395-Pyridin-3-yl-thiophene-2-carboxylic acid 3-(2-methyl-1,2,3,4-tetrahydro-isoquinolin-7-ylcarbamoyl)-benzylamideYield 87%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-pyridin-3-yl-thiophene-2-carboxylic acid (31 mg, 0.15 mmol) in DMF (1 mL) add Hunig's Base (0.10 mL, 0.54 mmol) and TBTU (52 mg, 0.16 mmol) and stir at rt for 20 min. To this add 3-aminomethyl-N-(2-methyl-1,2,3,4-tetrahydro-isoquinolin-7-yl)-benzamide dihydrochloride (50 mg, 0.1 mmol) and stir the solution for 18 h at rt. Concentrate the solution and purify the residue by prep-HPLC (10% to 90%, CH3CN/H2O) to provide the desired product 5-pyridin-3-yl-thiophene-2-carboxylic acid 3-(2-methyl-1,2,3,4-tetrahydro-isoquinolin-7-ylcarbamoyl)-benzylamide (62 mg, 0.087 mmol). MS, electrospray 483.8 (M+H), rt 0.88 min.

Workup

  1. concentrationConcentrate the solution
  2. custompurify the residue by prep-HPLC (10% to 90%, CH3CN/H2O)

Sources & evidence

ORD record
ord-de159192e99b4818929f2dd6146aee08
Source dataset
uspto-grants-2014_04
Patent number
US08697911B2

Reaction notes

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