Dimethylformamide → (2S)-N-(2-(2-Amino-1-(4-chlorophenyl)-2-oxoethyl)-1-oxo-1,2-dihydroisoquinolin-5-yl)-2-(4-chlorophenyl)propanamide

HRID 1161253Notes

Reaction equation

HRID 1161253 reaction equation
[NH2:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]([CH:13]([C:17]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=1)[C:14]([NH2:16])=[O:15])[C:7]2=[O:12].CN(C)C=O.C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.[Cl:62][C:63]1[CH:68]=[CH:67][C:66]([C@H:69]([CH3:73])[C:70](O)=[O:71])=[CH:65][CH:64]=1>>[NH2:16][C:14](=[O:15])[CH:13]([N:6]1[CH:5]=[CH:4][C:3]2[C:8](=[CH:9][CH:10]=[CH:11][C:2]=2[NH:1][C:70](=[O:71])[C@H:69]([C:66]2[CH:67]=[CH:68][C:63]([Cl:62])=[CH:64][CH:65]=2)[CH3:73])[C:7]1=[O:12])[C:17]1[CH:18]=[CH:19][C:20]([Cl:23])=[CH:21][CH:22]=1

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 7023129(2S)-2-(4-chlorophenyl)propanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 595158802-(5-Amino-1-oxoisoquinolin-2(1H)-yl)-2-(4-chlorophenyl)acetamide

Product 1

HCID 59515692(2S)-N-(2-(2-Amino-1-(4-chlorophenyl)-2-oxoethyl)-1-oxo-1,2-dihydroisoquinolin-5-yl)-2-(4-chlorophenyl)propanamide

Procedure

A round bottom flask was charged with 2-(5-amino-1-oxoisoquinolin-2(1H)-yl)-2-(4-chlorophenyl)acetamide (100 mg, 0.3 mmol), N,N-dimethylformamide (1 mL, 10 mmol), N,N-diisopropylethylamine (0.1 mL, 0.6 mmol), N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (200 mg, 0.6 mmol) and (S)-2-(4-chlorophenyl)propanoic acid (68 mg, 0.37 mmol) and the reaction stirred at room temperature over night. The solvent was removed and the residue purified by flash chromatography (12 g silica gel, 0-10% MeOH/DCM) followed by preparative HPLC (reverse phase) to obtain the product as an off white solid. MS m/z=477.1 (M+H). 1H NMR (400 MHz; DMSO-d6) δ 9.97 (s, 1H), 8.12-8.10 (d, J=8.18 Hz, 1H), 8.03 (s, 1H), 7.75-7.70 (dd, J=8.18&5.63 Hz, 1H), 7.59 (s, 1H), 7.501-7.34 (m, 9H), 7.03-7.00 (d, J=8.01 Hz, 1H), 6.71 (s, 1H), 6.40-6.38 (d, J=8.27 Hz, 1H), 4.00-3.94 (q, J=6.97 Hz, 1H), 1.44-1.41 (d, J=7.11 Hz, 3H).

Workup

  1. customThe solvent was removed
  2. customthe residue purified by flash chromatography (12 g silica gel, 0-10% MeOH/DCM)
  3. customto obtain the product as an off white solid

Sources & evidence

ORD record
ord-19342734a0dc439a8160ff6b1d1f8067
Source dataset
uspto-grants-2010_10
Patent number
US07816371B2

Reaction notes

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