Dimethylformamide → (S)-2-(5-(2-(4-Chloro-2-(trifluoromethyl)phenyl)acetamido)-1-oxoisoquinolin-2(1H)-yl)propanamide

HRID 1161201Notes

Reaction equation

HRID 1161201 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=O)=[C:4]([C:12]([F:15])([F:14])[F:13])[CH:3]=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.[NH2:54][C:55]1[CH:64]=[CH:63][CH:62]=[C:61]2[C:56]=1[CH:57]=[CH:58][N:59]([C@@H:66]([CH3:70])[C:67]([NH2:69])=[O:68])[C:60]2=[O:65]>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([NH:54][C:55]2[CH:64]=[CH:63][CH:62]=[C:61]3[C:56]=2[CH:57]=[CH:58][N:59]([C@@H:66]([CH3:70])[C:67]([NH2:69])=[O:68])[C:60]3=[O:65])=[O:11])=[C:4]([C:12]([F:15])([F:14])[F:13])[CH:3]=1

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 32777474-Chloro-2-(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 59515789(S)-2-(5-Amino-1-oxoisoquinolin-2(1H)-yl)propanamide

Product 1

HCID 59515761(S)-2-(5-(2-(4-Chloro-2-(trifluoromethyl)phenyl)acetamido)-1-oxoisoquinolin-2(1H)-yl)propanamide

Procedure

A round bottom flask was charged with 2-(4-chloro-2-(trifluoromethyl)phenyl)acetic acid (0.13 g, 0.00056 mol), N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (0.3 g, 0.0009 mol), N,N-diisopropylethylamine (0.2 mL, 0.0009 mol), N,N-dimethylformamide (5 mL, 0.06 mol) and (S)-2-(5-amino-1-oxoisoquinolin-2(1H)-yl)propanamide (0.1 g, 0.0004 mol), and the reaction was stirred for 16 h at room temperature. The reaction was quenched with water and extracted with dichloromethane, washed with 2N HCl, saturated sodium bicarbonate solution, brine and dried over sodium sulfate. The solvent was removed under reduced pressure and the residue purified by flash chromatography (12 g, 0-10% MeOH/DCM) to yield the product as a white solid. MS m/z=452.4 (M+H). 1H NMR (400 MHz; DMSO-d6) δ 10.11 (s, 1H), 8.07 (d, J=8.80 Hz, 1H), 7.79-7.76 (m, 3H) 7.64-7.60 (m, 2H), 7.49 (d, J=8.08 Hz, 1H), 7.45 (t, J=7.7 Hz, 1H), 7.23 (bs, 1H), 6.71 (d, J=7.77 Hz, 1H), 5.50-5.45 (q, J=7.24 Hz, 1H), 4.06 (s, 2H), 1.55 (d, J=7.54 Hz, 3H).

Workup

  1. customThe reaction was quenched with water
  2. extractionextracted with dichloromethane
  3. washwashed with 2N HCl, saturated sodium bicarbonate solution, brine
  4. dry with materialdried over sodium sulfate
  5. customThe solvent was removed under reduced pressure
  6. customthe residue purified by flash chromatography (12 g, 0-10% MeOH/DCM)

Sources & evidence

ORD record
ord-b2f457cf417b4581b8a241f2904dc394
Source dataset
uspto-grants-2010_10
Patent number
US07816371B2

Reaction notes

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