Diisopropylethylamine → 2-(4-Chloro-3-(trifluoromethyl)phenyl)-N-(1-oxo-2-(pyridin-2-ylmethyl)-1,2-dihydroisoquinolin-5-yl)acetamide

HRID 1037782Notes

Reaction equation

HRID 1037782 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]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=1)[C:7]2=[O:12].[Cl:20][C:21]1[CH:26]=[CH:25][C:24]([CH2:27][C:28](O)=[O:29])=[CH:23][C:22]=1[C:31]([F:34])([F:33])[F:32].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=O)C>[Cl:20][C:21]1[CH:26]=[CH:25][C:24]([CH2:27][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]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)[C:7]3=[O:12])=[O:29])=[CH:23][C:22]=1[C:31]([F:32])([F:33])[F:34]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 35198824-Chloro-3-(trifluoromethyl)phenylacetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 595793535-Amino-2-(pyridin-2-ylmethyl)isoquinolin-1(2H)-one

Product 1

HCID 595793842-(4-Chloro-3-(trifluoromethyl)phenyl)-N-(1-oxo-2-(pyridin-2-ylmethyl)-1,2-dihydroisoquinolin-5-yl)acetamideYield 71.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
50 °C

Procedure

To a solution of 5-amino-2-(pyridin-2-ylmethyl)isoquinolin-1(2H)-one (100.00 mg, 0.4 mmol) in N,N-dimethylformamide (0.7 mL, 0.009 mol) was added 2-(4-chloro-3-(trifluoromethyl)phenyl)acetic acid (190 mg, 0.000796 mol), N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (303 mg, 0.000796 mol) and N,N-diisopropylethylamine (277 uL, 0.00159 mol). The reaction mixture was stirred for 16 hours at 50° C. Checked LC/MS, the reaction was completed. The DMF reaction solution was directly applied to prep. HPLC to obtain the pure product (134.2 mg). MS m/z=472.3 (M+1). 1H NMR (DMSO) δ 10.13 (s, 1 H), 8.48 (d, J=4.8 Hz, 1 H), 8.06 (d, J=7/9 Hz, 1 H), 7.90 (s, 1 H), 7.84 (d, J=7.1 Hz, 1 H), 7.76 (td, J=7.7, 1.8 Hz, 1 H), 7.75-7.68 (m, 2 H), 7.63 (d, J=7.7 Hz, 1 H), 7.47 (t, J=7.9 Hz, 1 H), 7.32-7.22 (m, 2 H), 6.73 (d, J=7.6 Hz, 1 H), 5.28 (s, 2 H), 3.93 (s, 2 H).

Sources & evidence

ORD record
ord-6896b81decdb455c95b2818483f37b23
Source dataset
uspto-grants-2013_10
Patent number
US08546579B2

Reaction notes

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