Dimethylformamide → (S)-N-(2-((R)-2-Amino-2-oxo-1-phenylethyl)-1-oxo-1,2-dihydroisoquinolin-5-yl)-2-(3,4-dichlorophenyl)-propanamide

HRID 1161236Notes

Reaction equation

HRID 1161236 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]([C@H:13]([C:17]1[CH:22]=[CH:21][CH:20]=[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:61][C:62]1[CH:63]=[C:64]([C@H:69]([CH3:73])[C:70](O)=[O:71])[CH:65]=[CH:66][C:67]=1[Cl:68]>>[NH2:16][C:14](=[O:15])[C@H: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:64]2[CH:65]=[CH:66][C:67]([Cl:68])=[C:62]([Cl:61])[CH:63]=2)[CH3:73])[C:7]1=[O:12])[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 28292773(S)-2-(3,4-dichlorophenyl)propanoic acidHCID 59515654(R)-2-(5-Amino-1-oxoisoquinolin-2(1H)-yl)-2-phenylacetamide

Product 1

HCID 59515817(S)-N-(2-((R)-2-Amino-2-oxo-1-phenylethyl)-1-oxo-1,2-dihydroisoquinolin-5-yl)-2-(3,4-dichlorophenyl)-propanamide

Procedure

A round bottom flask was charged with (R)-2-(5-amino-1-oxoisoquinolin-2(1H)-yl)-2-phenylacetamide (120 mg, 0.00041 mol), N,N-dimethylformamide (1.5 mL, 0.019 mol), N,N-diisopropylethylamine (0.1 mL, 0.0008 mol), N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (0.3 g, 0.0008 mol) and (S)-2-(3,4-dichlorophenyl)propanoic acid (0.11 g, 0.00049 mol) and the reaction stirred at room temperature overnight. The solvent was removed and the residue purified by flash chromatography and again by preparative HPLC (reverse phase) to obtain the product as a white solid. MS m/z=495.2 (M+H). 1H NMR (400 MHz; DMSO-d6) δ 9.98 (s, 1H), 8.13-8.11 (d, J=8.37 Hz, 1H), 8.03 (s, 1H), 7.74-7.72 (d, J=7.90 Hz, 1H), 7.64-7.63 (d, J=2.06 Hz, 1H), 7.61-7.59 (d, J=7.94 Hz, 1H), 7.55 (s, 1H), 7.50-7.33 (m, 6H), 7.00-6.98 (d, J=8.02 Hz, 1H), 6.74 (s, 1H), 6.39-6.37 (d, J=8.02 Hz, 1H), 4.02-3.96 (q, J=7.01 Hz, 1H), 1.45-1.43 (d, J=7.55 Hz, 3H).

Workup

  1. customThe solvent was removed
  2. customthe residue purified by flash chromatography and again by preparative HPLC (reverse phase)

Sources & evidence

ORD record
ord-19884ef2b8f445b082baa59036928c15
Source dataset
uspto-grants-2010_10
Patent number
US07816371B2

Reaction notes

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