Dimethylformamide → furan-2-carboxylic acid (7-benzo[b]thiophen-2-yl-1H-indazol-5-yl)-amide

HRID 1678212Notes

Reaction equation

HRID 1678212 reaction equation
CN1CCOCC1.[O:8]1[CH:12]=[CH:11][CH:10]=[C:9]1[C:13]([OH:15])=O.[S:16]1[C:20]([C:21]2[CH:22]=[C:23]([NH2:30])[CH:24]=[C:25]3[C:29]=2[NH:28][N:27]=[CH:26]3)=[CH:19][C:18]2[CH:31]=[CH:32][CH:33]=[CH:34][C:17]1=2.CN(C=O)C>CC#N.C(Cl)Cl.CC#N>[S:16]1[C:20]([C:21]2[CH:22]=[C:23]([NH:30][C:13]([C:9]3[O:8][CH:12]=[CH:11][CH:10]=3)=[O:15])[CH:24]=[C:25]3[C:29]=2[NH:28][N:27]=[CH:26]3)=[CH:19][C:18]2[CH:31]=[CH:32][CH:33]=[CH:34][C:17]1=2

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 69192-Furancarboxylic acidHCID 79724-MethylmorpholineHCID 59023728HCID 59023728, compound

Product 1

HCID 59023896furan-2-carboxylic acid (7-benzo[b]thiophen-2-yl-1H-indazol-5-yl)-amideYield 4.7%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 21877088Acetonitrile methylene chlorideSolvent2×

Procedure

In a 20 mL vial, a solution of N-methylmorpholine (0.060 g, 0.60 mmol) in MeCN/CH2Cl2 (1:1, 0.688 mL) was added to Si-dichlorotriazine (SiliCycle, Inc; 0.60 mmol/g, 0.74 g, 0.44 mmol). Then, a solution of 2-furoic acid (0.021 g, 0.19 mmol) in MeCN (0.925 mL) was added and mixed for about 1 min., prior to the addition of a solution of 7-benzo[b]thiophen-2-yl-1H-indazol-5-ylamine (Example #F.8.1, 0.039 g, 0.15 mmol) in MeCN/CH2Cl2 (1:1, 0.688 mL). The reaction mixture was shaken at ambient temperature for about 16 hours. The crude reaction solution was mixed with DMF (5 mL) to aid in solubility, eluted through a Si-carbonate (SiliCycle, Inc; 1 g, 6 mL) cartridge using MeOH (approx 3 mL), and concentrated in vacuo. The crude product was then purified by preparative HPLC (Waters Symmetry C8 column (25×100 mm, 7 μm particle size) using a gradient of 10%-100% CH3CN/0.1% aqueous TFA over 8 min (10 min run time) at a flow rate of 40 mL/min) to afford furan-2-carboxylic acid (7-benzo[b]thiophen-2-yl-1H-indazol-5-yl)-amide (0.0025 g, 4.7%); RP-HPLC (Table 1, Method 1) Rt 2.51 min; m/z: (M+H)+ 360.

Workup

  1. additionmixed for about 1 min.
  2. customThe crude reaction solution
  3. washeluted through a Si-carbonate (SiliCycle, Inc; 1 g, 6 mL) cartridge
  4. concentrationconcentrated in vacuo
  5. customThe crude product was then purified by preparative HPLC (Waters Symmetry C8 column (25×100 mm, 7 μm particle size)
  6. customover 8 min
  7. custom(10 min run time)

Sources & evidence

ORD record
ord-54ed6f4050f7407caa9cbb83934feefa
Source dataset
uspto-grants-2011_08
Patent number
US08008481B2

Reaction notes

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