Dimethylformamide → (R)-2-(5-((S)-2-(4-Chlorophenyl)propanamido)-1-oxoisoquinolin-2(1H)-yl)-N,3-dimethylbutanamide

HRID 1161233Notes

Reaction equation

HRID 1161233 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]([NH: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]([NH: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 59515790(R)-2-(5-Amino-1-oxoisoquinolin-2(1H)-yl)-N,3-dimethylbutanamide

Product 1

HCID 59515852(R)-2-(5-((S)-2-(4-Chlorophenyl)propanamido)-1-oxoisoquinolin-2(1H)-yl)-N,3-dimethylbutanamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

(R)-2-(5-Amino-1-oxoisoquinolin-2(1H)-yl)-N,3-dimethylbutanamide (0.2 g, 0.0007 mol), (S)-2-(4-chlorophenyl)propanoic acid (0.16 g, 0.00088 mol), N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (0.56 g, 0.0015 mol), N,N-diisopropylethylamine (0.4 g, 0.003 mol) were stirred in methylene chloride (3 mL, 0.05 mol) and N,N-dimethylformamide (1 mL, 0.01 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 yielded a white solid. 1H NMRδ (CDCl3) δ: 9.23 (d, J=8.1 Hz, 1H), 8.00 (t, J=7.5 Hz, 1H), 7.52-7.36 (m, 6H), 7.04 (br, 1H), 6.17 (br, 1H), 6.03-6.00 (m, 1H), 5.07 (d, J=11.4 Hz, 1H), 3.82 (q, J=7.0 Hz, 1H), 2.76 (d, J=4.8 Hz, 3H), 2.56-2.48 (m, 1H), 1.65 (dd, J=1.8, 7.1 Hz, 3H), 1.06 (d, J=6.4 Hz, 3H), 0.75 (dd, J=2.6, 6.6 Hz, 3H). MS m/z 440.0 (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 yielded a white solid

Sources & evidence

ORD record
ord-d0d4bf5ca8dc46a391544294b08785e9
Source dataset
uspto-grants-2010_10
Patent number
US07816371B2

Reaction notes

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