4-Methylmorpholine → 3'-Hydroxy-biphenyl-4-carboxylic acid 3-(2-methyl-1,2,3,4-tetrahydro-isoquinolin-7-ylcarbamoyl)-benzylamide

HRID 2367738Notes

Reaction equation

HRID 2367738 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([OH:16])=O)=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.Cl.[NH2:43][CH2:44][C:45]1[CH:46]=[C:47]([CH:62]=[CH:63][CH:64]=1)[C:48]([NH:50][C:51]1[CH:60]=[C:59]2[C:54]([CH2:55][CH2:56][N:57]([CH3:61])[CH2:58]2)=[CH:53][CH:52]=1)=[O:49].CN1CCOCC1>CN(C=O)C>[CH3:61][N:57]1[CH2:56][CH2:55][C:54]2[C:59](=[CH:60][C:51]([NH:50][C:48]([C:47]3[CH:46]=[C:45]([CH:64]=[CH:63][CH:62]=3)[CH2:44][NH:43][C:14]([C:11]3[CH:10]=[CH:9][C:8]([C:4]4[CH:5]=[CH:6][CH:7]=[C:2]([OH:1])[CH:3]=4)=[CH:13][CH:12]=3)=[O:16])=[O:49])=[CH:52][CH:53]=2)[CH2:58]1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 27593023'-Hydroxybiphenyl-4-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 666490723-(2-Methyl-1,2,3,4-tetrahydro-isoquinolin-7-ylcarbamoyl)benzylamine dihydrochloride

Product 1

HCID 566003433'-Hydroxy-biphenyl-4-carboxylic acid 3-(2-methyl-1,2,3,4-tetrahydro-isoquinolin-7-ylcarbamoyl)-benzylamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a vial containing 3′-hydroxy-biphenyl-4-carboxylic acid (26 mg, 0.12 mmol) add a solution of HATU (2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate) (57 mg, 0.15 mmol) in DMF (1 mL) followed by a solution of 3-aminomethyl-N-(2-methyl-1,2,3,4-tetrahydro-isoquinolin-7-yl)-benzamide dihydrochloride (37 mg, 0.10 mmol) and 4-methylmorpholine (0.044 mL, 0.40 mmol) in DMF (1 mL). Shake the reaction at rt for 24 h. Concentrate in vacuo to an oil. Dissolve the residue in 10% water in DMSO (0.9 mL) and purify by prep-HPLC (10% to 90%, CH3CN/H2O). Concentrate fractions to afford the desired product 3′-hydroxy-biphenyl-4-carboxylic acid 3-(2-methyl-1,2,3,4-tetrahydro-isoquinolin-7-ylcarbamoyl)-benzylamide as a solid in 45% yield (22 mg, 0.045 mmol). MS, electrospray (M+H) 492.4, rt 2.29 min.

Workup

  1. customShake the reaction at rt for 24 h
  2. concentrationConcentrate in vacuo to an oil
  3. dissolutionDissolve the residue in 10% water in DMSO (0.9 mL)
  4. custompurify by prep-HPLC (10% to 90%, CH3CN/H2O)

Sources & evidence

ORD record
ord-d37fc8aad8794e2c9b5727282966f984
Source dataset
uspto-grants-2014_04
Patent number
US08697911B2

Reaction notes

Loading…