Diisopropylethylamine → (S)-2-(6-Chloro-1-oxo-5-(2-(4-(trifluoromethyl)phenyl)acetamido)isoquinolin-2(1H)-yl)propanamide

HRID 1161270Notes

Reaction equation

HRID 1161270 reaction equation
[NH2:1][C:2]1[C:11]([Cl:12])=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]([C@@H:14]([CH3:18])[C:15]([NH2:17])=[O:16])[C:7]2=[O:13].[F:19][C:20]([F:32])([F:31])[C:21]1[CH:26]=[CH:25][C:24]([CH2:27][C:28](O)=[O:29])=[CH:23][CH:22]=1.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:12][C:11]1[C:2]([NH:1][C:28](=[O:29])[CH2:27][C:24]2[CH:23]=[CH:22][C:21]([C:20]([F:31])([F:19])[F:32])=[CH:26][CH:25]=2)=[C:3]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:13])[N:6]([C@@H:14]([CH3:18])[C:15]([NH2:17])=[O:16])[CH:5]=[CH:4]2

Participants

5

Reactant 4

HCID 81531DiisopropylethylamineHCID 118342(alpha,alpha,alpha-Trifluoro-4-tolyl)acetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58973961(S)-2-(5-Amino-6-chloro-1-oxoisoquinolin-2(1H)-yl)propanamide

Product 1

HCID 25013760(S)-2-(6-Chloro-1-oxo-5-(2-(4-(trifluoromethyl)phenyl)acetamido)isoquinolin-2(1H)-yl)propanamide

Conditions

Temperature
60 °C

Procedure

A mixture of (S)-2-(5-amino-6-chloro-1-oxoisoquinolin-2(1H)-yl)propanamide (100.0 mg, 0.0003764 mol), 2-(4-(trifluoromethyl)phenyl)acetic acid (115.2 mg, 0.0005646 mol), N,N-diisopropylethylamine (163.9 μL, 0.0009409 mol), N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (357.8 mg, 0.0009409 mol) and N,N-dimethylfonnamide (2 mL, 0.02 mol) was stirred at 60° C. for 3 days. The reaction was only about 40% complete. The solvent was removed and the residue purified by preparative HPLC (reverse phase) to obtain the product as light yellow solid. MS m/z=452.1 (M+H). 1H NMR (400 MHz; DMSO-d6) δ10.21 (s, 1H), 8.15 (d, J=8.68 Hz, 1H), 7.74 (d, J=7.76 Hz, 2H), 7.66-7.58 (m, 4H), 7.49 (d, J=7.95 Hz, 1H), 7.25 (s, 1H), 6.43 (d, J=7.50 Hz, 1H), 5.47-5.42 (q, J=7.07 Hz, 1H), 3.90 (s, 2H), 1.53 (d, J=7.39 Hz, 3H).

Workup

  1. customThe solvent was removed
  2. customthe residue purified by preparative HPLC (reverse phase)

Sources & evidence

ORD record
ord-0b863fcad4eb4687ba0ee6d3e301cc06
Source dataset
uspto-grants-2010_10
Patent number
US07816371B2

Reaction notes

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