Dimethylformamide → (R)-Methyl 2-(5-((S)-2-(4-chlorophenyl)propanamido)-1-oxoisoquinolin-2(1H)-yl)-3-methylbutanoate

HRID 1161260Notes

Reaction equation

HRID 1161260 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]([CH:18]([CH3:20])[CH3:19])[C:14]([O:16][CH3:17])=[O:15])[C:7]2=[O:12].[Cl:21][C:22]1[CH:27]=[CH:26][C:25]([C@H:28]([CH3:32])[C:29](O)=[O:30])=[CH:24][CH:23]=1.F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.CN(C)C=O>C(Cl)Cl>[Cl:21][C:22]1[CH:23]=[CH:24][C:25]([C@H:28]([CH3:32])[C:29]([NH:1][C:2]2[CH:11]=[CH:10][CH:9]=[C:8]3[C:3]=2[CH:4]=[CH:5][N:6]([C@H:13]([CH:18]([CH3:20])[CH3:19])[C:14]([O:16][CH3:17])=[O:15])[C:7]3=[O:12])=[O:30])=[CH:26][CH:27]=1

Participants

7

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 59515897(R)-Methyl 2-(5-amino-1-oxoisoquinolin-2(1H)-yl)-3-methylbutanoate

Product 1

HCID 59515742(R)-Methyl 2-(5-((S)-2-(4-chlorophenyl)propanamido)-1-oxoisoquinolin-2(1H)-yl)-3-methylbutanoate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(R)-Methyl 2-(5-amino-1-oxoisoquinolin-2(1H)-yl)-3-methylbutanoate (0.3 g, 0.001 mol), (S)-2-(4-chlorophenyl)propanoic acid (0.4 g, 0.002 mol), N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (0.8 g, 0.002 mol), N,N-diisopropylethylamine (0.6 g, 0.004 mol) were stirred in N,N-dimethylformamide (3 mL, 0.04 mol) at room temperature over a weekend. The reaction mixture was diluted with CH2Cl2 (100 mL), washed with NaHCO3 (20 mL×3), dried over Na2SO4, purified via flash chromatography (12 g of silica gel, 0-90% EtOAc/Hexane) and then prep. HPLC gave a light yellow oil. MS m/z 441.3 (M+H)+.

Workup

  1. washwashed with NaHCO3 (20 mL×3)
  2. dry with materialdried over Na2SO4
  3. custompurified via flash chromatography (12 g of silica gel, 0-90% EtOAc/Hexane)
  4. customHPLC gave a light yellow oil

Sources & evidence

ORD record
ord-e734999a99754b01a1c42e02ce0ca490
Source dataset
uspto-grants-2010_10
Patent number
US07816371B2

Reaction notes

Loading…