4-(2-(Tributylstannyl)pyrimidin-4-yl)morpholine → tert-butyl 5-(5-(methylthio)-1,3,4-thiadiazol-2-yl)-3-(4-morpholinopyrimidin-2-yl)-1H-indole-1-carboxylate

HRID 634123Notes

Reaction equation

HRID 634123 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][CH3:17])=[N:14][N:15]=3)[CH:9]=2)[N:4]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH:3]=1.C([Sn](CCCC)(CCCC)[C:30]1[N:35]=[C:34]([N:36]2[CH2:41][CH2:40][O:39][CH2:38][CH2:37]2)[CH:33]=[CH:32][N:31]=1)CCC>CN(C=O)C.[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>[CH3:17][S:16][C:13]1[S:12][C:11]([C:8]2[CH:9]=[C:10]3[C:5](=[CH:6][CH:7]=2)[N:4]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH:3]=[C:2]3[C:30]2[N:35]=[C:34]([N:36]3[CH2:41][CH2:40][O:39][CH2:38][CH2:37]3)[CH:33]=[CH:32][N:31]=2)=[N:15][N:14]=1

Participants

6

Reactant 2

HCID 683283544-(2-(Tributylstannyl)pyrimidin-4-yl)morpholineHCID 68328746tert-butyl 3-iodo-5-(5-(methylthio)-1,3,4-thiadiazol-2-yl)-1H-indole-1-carboxylate

Product 1

HCID 68327968tert-butyl 5-(5-(methylthio)-1,3,4-thiadiazol-2-yl)-3-(4-morpholinopyrimidin-2-yl)-1H-indole-1-carboxylateYield 20%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of tert-butyl 3-iodo-5-(5-(methylthio)-1,3,4-thiadiazol-2-yl)-1H-indole-1-carboxylate (1.2 g, 2.5 mmol) and 4-(2-(tributylstannyl)pyrimidin-4-yl)morpholine (1.38 g, 4.0 mmol) in DMF (10 mL) was added CuI (0.62 g, 3.2 mmol) and Pd(PPh3)4 (0.29 g, 0.25 mmol). The mixture was purged with Ar for 5 min then heated at 90° C. for 1 h. The mixture was poured into H2O and the aqueous layer was extracted with Et2O. The combined organic layers were dried, filtered and concentrated. The residue was purified with flash chromatography to give tert-butyl 5-(5-(methylthio)-1,3,4-thiadiazol-2-yl)-3-(4-morpholinopyrimidin-2-yl)-1H-indole-1-carboxylate (255 mg, 20%). MS (ESI, pos. ion) m/z: 511.1 (M+1). 1H-NMR (DMSO-d6, 300 MHz) δ: 9.12 (1H, d), 8.39 (2H, brs), 8.25 (1H, d), 7.9 (1H, dd), 6.79 (1H, d). 3.7-3.85 (8H, brs), 2.85 (3H, s), 1.65 (9H, s).

Workup

  1. customThe mixture was purged with Ar for 5 min
  2. additionThe mixture was poured into H2O
  3. extractionthe aqueous layer was extracted with Et2O
  4. customThe combined organic layers were dried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified with flash chromatography

Sources & evidence

ORD record
ord-5094efc520ed43a19d61f478c2d6eda8
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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