Dimethylformamide → (3e)-5,6-Difluoro-3-[4-(4-{[4-(2-hydroxyethyl)piperazin-1-yl]carbonyl}phenyl)-5,5-dimethylfuran-2(5h)-ylidene]-1,3-dihydro-2h-indol-2-one

HRID 333373Notes

Reaction equation

HRID 333373 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5](/[C:6](=[C:12]3/[CH:13]=[C:14]([C:19]4[CH:27]=[CH:26][C:22]([C:23](O)=[O:24])=[CH:21][CH:20]=4)[C:15]([CH3:18])([CH3:17])[O:16]/3)/[C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1.C[CH2:29][N:30]([CH:34](C)C)C(C)C.[F:37][P-](F)(F)(F)(F)F.N1(O[C:54]([N:58]([CH3:60])[CH3:59])=[N+](C)C)C2C=CC=CC=2N=N1.CN([CH:64]=[O:65])C>>[F:37][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:2]=1[F:1])[NH:8][C:7](=[O:11])/[C:6]/2=[C:12]1/[O:16][C:15]([CH3:17])([CH3:18])[C:14]([C:19]2[CH:27]=[CH:26][C:22]([C:23]([N:30]3[CH2:34][CH2:59][N:58]([CH2:54][CH2:64][OH:65])[CH2:60][CH2:29]3)=[O:24])=[CH:21][CH:20]=2)=[CH:13]/1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 589262664-[(5E)-5-(6-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)-2,2-dimethyl-2,5-dihydrofuran-3-yl]benzoic acid

Product 1

HCID 58926189(3e)-5,6-Difluoro-3-[4-(4-{[4-(2-hydroxyethyl)piperazin-1-yl]carbonyl}phenyl)-5,5-dimethylfuran-2(5h)-ylidene]-1,3-dihydro-2h-indol-2-one

Procedure

To an 8-mL screw cap vial was added 4-[(5E)-5-(6-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)-2,2-dimethyl-2,5-dihydrofuran-3-yl]benzoic acid (58.5 mg, 0.16 mmol), amine (0.24 mmol, 1.5 eq.), DMF (1 mL), and DIPEA (0.06 mL, 0.35 mmol, 2.2 eq.), and O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HBTU) (91 mg, 0.24 mmol, 1.5 eq). The reaction mixture was shaken at room temperature for 24 hours. The resulting clear reaction mixture was submitted for preparative RP-HPLC purification without workup. The library compounds were purified by high throughput RP-HPLC. Each compound was re-analyzed by LCMS after purification.

Workup

  1. customTo an 8-mL screw cap
  2. customThe resulting clear reaction mixture was submitted for preparative RP-HPLC purification without workup
  3. customThe library compounds were purified by high throughput RP-HPLC
  4. customafter purification

Sources & evidence

ORD record
ord-cf8de1b52f8947d3bdae77ad1eedbaf6
Source dataset
uspto-grants-2014_11
Patent number
US08877923B2

Reaction notes

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