Dimethylformamide → (R)-2-(5-((R)-2-(4-Chlorophenyl)propanamido)-1-oxoisoquinolin-2(1H)-yl)-3-methylbutanamide

HRID 1161245Notes

Reaction equation

HRID 1161245 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:17]([CH3:19])[CH3:18])[C:14]([NH2:16])=[O:15])[C:7]2=[O:12].[Cl:20][C:21]1[CH:26]=[CH:25][C:24]([C@@H:27]([CH3:31])[C:28](O)=[O:29])=[CH:23][CH:22]=1.C(N(CC)C(C)C)(C)C.CN(C)C=O>C(Cl)Cl>[Cl:20][C:21]1[CH:22]=[CH:23][C:24]([C@@H:27]([CH3:31])[C:28]([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:17]([CH3:19])[CH3:18])[C:14]([NH2:16])=[O:15])[C:7]3=[O:12])=[O:29])=[CH:25][CH:26]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 7568437(R)-2-(4-chlorophenyl)propanoic acidHCID 59515872(R)-2-(5-Amino-1-oxoisoquinolin-2(1H)-yl)-3-methylbutanamide

Product 1

HCID 52914142(R)-2-(5-((R)-2-(4-Chlorophenyl)propanamido)-1-oxoisoquinolin-2(1H)-yl)-3-methylbutanamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(R)-2-(5-Amino-1-oxoisoquinolin-2(1H)-yl)-3-methylbutanamide (0.2 g, 0.0007 mol), (R)-2-(4-chlorophenyl)propanoic acid (0.16 g, 0.00088 mol) N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (0.33 g, 0.00088 mol), N,N-diisopropylethylamine (0.4 g, 0.003 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 white solid. 1H NMR δ (CDCl3) δ: 8.24 (d, J=8.1 Hz, 1H), 7.99 (t, J=7.2 Hz, 1H), 7.53-7.33 (m, 6H), 7.07 (br, 1H), 6.26 (br, 1H), 6.06-6.03 (m, 1H), 5.31 (br, 1H), 5.14 (d, J=11.4 Hz, 1H), 3.82 (q, J=7.2 Hz, 1H), 2.55-2.48 (m, 1H), 1.62 (d, J=11.1 Hz, 3H), 1.13 (d, J=6.4 Hz, 3H), 0.76 (dd, J=2.1, 6.6 Hz, 3H). MS m/z 426.2 (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 white solid

Sources & evidence

ORD record
ord-c3e781b90d28400daffa448390b81421
Source dataset
uspto-grants-2010_10
Patent number
US07816371B2

Reaction notes

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