Dimethylformamide → HCID 25013601, compound

HRID 1161256Notes

Reaction equation

HRID 1161256 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].CN(C)C=O.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.[F:57][C:58]([F:70])([F:69])[C:59]1[CH:64]=[CH:63][C:62]([CH2:65][C:66](O)=[O:67])=[CH:61][CH:60]=1>>[Cl:12][C:11]1[C:2]([NH:1][C:66](=[O:67])[CH2:65][C:62]2[CH:61]=[CH:60][C:59]([C:58]([F:69])([F:57])[F:70])=[CH:64][CH:63]=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

6

Reactant 5

HCID 6228DimethylformamideHCID 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 59515791(R)-2-(5-Amino-6-chloro-1-oxoisoquinolin-2(1H)-yl)propanamide

Product 1

HCID 25013601HCID 25013601, compound

Procedure

A round bottom flask was charged with (R)-2-(5-amino-6-chloro-1-oxoisoquinolin-2(1H)-yl)propanamide (50 mg, 0.0002 mol), N,N-dimethylformamide (1 mL, 0.01 mol), N,N-diisopropylethylamine (60 μL, 0.0004 mol), N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (100 mg, 0.0004 mol) and 2-(4-(trifluoromethyl)phenyl)acetic acid (46 mg, 0.00022 mol) and the reaction stirred at room temperature overnight. The reaction was only 60% complete. Stirring for an additional 6 hours did not improve the reaction. The solvent was removed and the residue purified by preparative HPLC (reverse phase) to obtain the product as an off white solid. MS m/z=452.2 (M+H). 1H NMR (400 MHz; DMF) δ 10.41 (s, 1H), 8.34 (d, J=8.71 Hz, 1H), 7.93 (d, J=8.22 Hz, 1H), 7.84 (d, J=10.96 Hz, 1H), 7.80 (t, J=9.13 Hz, 1H), 7.68 (d, J=8.53 Hz, 1H), 7.44 (bs, 1H), 6.62 (d, J=7.89 Hz, 1H), 5.67-5.61 (q, J=7.24 Hz, 1H), 4.09 (s, 2H), 1.72 (d, J=7.50 Hz, 3H).

Workup

  1. stirringStirring for an additional 6 hours
  2. customthe reaction
  3. customThe solvent was removed
  4. customthe residue purified by preparative HPLC (reverse phase)
  5. customto obtain the product as an off white solid

Sources & evidence

ORD record
ord-f39c0fbd5e914559a8c72b63a9d6f9e3
Source dataset
uspto-grants-2010_10
Patent number
US07816371B2

Reaction notes

Loading…