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

HRID 1161239Notes

Reaction equation

HRID 1161239 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:67]=[CH:66][C:65]([C@H:68]([CH3:72])[C:69](O)=[O:70])=[CH:64][CH:63]=1>>[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:69](=[O:70])[C@H:68]([C:65]2[CH:66]=[CH:67][C:62]([Cl:61])=[CH:63][CH:64]=2)[CH3:72])[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 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 59515654(R)-2-(5-Amino-1-oxoisoquinolin-2(1H)-yl)-2-phenylacetamide

Product 1

HCID 52914237(S)-N-(2-((R)-2-Amino-2-oxo-1-phenylethyl)-1-oxo-1,2-dihydroisoquinolin-5-yl)-2-(4-chlorophenyl)-propanamide

Procedure

A mixture of (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-(4-chlorophenyl)propanoic acid (0.091 g, 0.00049 mol) was allowed to stir over night at room temperature. The solvent was removed and the residue purified by flash chromatography (12 g silica gel, 0-10% MeOH/DCM) and again by preparative HPLC (reverse phase) to obtain the product as an off white solid. MS m/z=460.3 (M+H). 1H NMR (400 MHz; DMSO-d6) δ 9.95 (s, 1H), 8.13-8.11 (d, J=7.99 Hz, 1H), 8.02 (s, 1H), 7.74-7.72 (d, J=7.60 Hz, 1H), 7.71-7.69 (d, J=8.03 Hz, 1H), 7.55 (s, 1H), 7.50-7.32 (m, 10H), 6.99-6.97 (dd, J=7.89&1.86 Hz, 1H), 6.74 (s, 1H), 6.39-6.37 (d, J=8.02 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) and again by preparative HPLC (reverse phase)
  3. customto obtain the product as an off white solid

Sources & evidence

ORD record
ord-6ca8a40150d645bdae667e298a14ae96
Source dataset
uspto-grants-2010_10
Patent number
US07816371B2

Reaction notes

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