HCID 22031857, compound → HCID 68328781, compound

HRID 634130Notes

Reaction equation

HRID 634130 reaction equation
I[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[S:12][C:13]([S:16]([CH3:19])(=[O:18])=[O:17])=[N:14][N:15]=3)[CH:9]=2)[N:4]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH:3]=1.[CH3:27][N:28]1[CH2:33][CH2:32][N:31]([C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([Sn](CCCC)(CCCC)CCCC)[N:35]=2)[CH2:30][CH2:29]1>[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:27][N:28]1[CH2:29][CH2:30][N:31]([C:34]2[N:35]=[C:36]([C:2]3[C:10]4[C:5](=[CH:6][CH:7]=[C:8]([C:11]5[S:12][C:13]([S:16]([CH3:19])(=[O:18])=[O:17])=[N:14][N:15]=5)[CH:9]=4)[N:4]([C:20]([O:22][C:23]([CH3:24])([CH3:26])[CH3:25])=[O:21])[CH:3]=3)[CH:37]=[CH:38][CH:39]=2)[CH2:32][CH2:33]1

Participants

5

Reactant 2

HCID 22031857HCID 22031857, compoundHCID 68328077HCID 68328077, compound

Product 1

HCID 68328781HCID 68328781, compoundYield 62.9%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Procedure

A solution of tert-butyl 3-iodo-5-(5-(methylsulfonyl)-1,3,4-thiadiazol-2-yl)-1H-indole-1-carboxylate (650 mg, 1.146 mmol) and 1-methyl-4-(6-(tributylstannyl)pyridin-2-yl)piperazine (596 mg, 1.146 mmol) DMF (10 mL) was purged the Argon gas for 5 min. To the solution was added CuI (327.5 mg, 1.71 mmol), Pd(PPh3)4 (159 mg, 0.137 mmol) and again the mixture was purged the Argon gas for 5 min. The mixture was stirred at RT for 2 h, then at 90° C. for 1 h. The mixture was poured into H2O and was extracted with EtOAc. The combined organic layer was dried, filtered and concentrated. The residue was purified with silica gel chromatography to give tert-butyl 3-(6-(4-methylpiperazin-1-yl)pyridin-2-yl)-5-(5-(methylsulfonyl)-1,3,4-thiadiazol-2-yl)-1H-indole-1-carboxylate (400 mg, 53.5%). MS (ESI, pos. ion) m/z: 555.1 (M+1); 1H-NMR (DMSO-d6, 300 MHz) δ: 9.245 (1H, s), 8.45 (1H, s), 8.35 (1H, d), 8.07 (1H, d), 7.65 (1H, m), 7.4 (1H, d), 6.85 (1H, d), 3.7-3.8 (3H, s), 3.7 (2H, brs), 2.3 (3H, s), 1.75 (9H, s), 1.2-1.3 (6H, m).

Workup

  1. customagain the mixture was purged the Argon gas for 5 min
  2. waitat 90° C. for 1 h
  3. additionThe mixture was poured into H2O
  4. extractionwas extracted with EtOAc
  5. customThe combined organic layer was dried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified with silica gel chromatography

Sources & evidence

ORD record
ord-a093555b2b424e7b85092b71bef6781c
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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