5-fluoro-4-(trimethylstannyl)-1H-indole → 2-(5-Fluoro-1H-indol-4-yl)-4-morpholin-4-yl-6-piperazin-1-ylmethyl-thieno[3,2-d]pyrimidine

HRID 2365205Notes

Reaction equation

HRID 2365205 reaction equation
[F:1][C:2]1[C:3]([Sn](C)(C)C)=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2.C(OC([N:22]1[CH2:27][CH2:26][N:25]([CH2:28][C:29]2[S:37][C:36]3[C:35]([N:38]4[CH2:43][CH2:42][O:41][CH2:40][CH2:39]4)=[N:34][C:33](SC)=[N:32][C:31]=3[CH:30]=2)[CH2:24][CH2:23]1)=O)(C)(C)C>C1COCC1.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>[F:1][C:2]1[C:3]([C:33]2[N:34]=[C:35]([N:38]3[CH2:39][CH2:40][O:41][CH2:42][CH2:43]3)[C:36]3[S:37][C:29]([CH2:28][N:25]4[CH2:26][CH2:27][NH:22][CH2:23][CH2:24]4)=[CH:30][C:31]=3[N:32]=2)=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2

Participants

5

Reactant 2

HCID 591512605-fluoro-4-(trimethylstannyl)-1H-indoleHCID 68717795HCID 68717795, compound

Product 1

HCID 249373842-(5-Fluoro-1H-indol-4-yl)-4-morpholin-4-yl-6-piperazin-1-ylmethyl-thieno[3,2-d]pyrimidineYield 10%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
90 °C

Procedure

A solution of 5-fluoro-4-(trimethylstannyl)-1H-indole (100 mg, 0.33 mmol), 4-(2-methylsulfanyl-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-piperazine-1-carboxylic acid tert-butyl ester (71 mg, 0.15 mmol) and copper(I) bromide-dimethyl sulfide complex (70 mg, 0.33 mmol) in THF (3 mL) was degassed with argon, treated with tetrakis(triphenylphosphine)palladium(0) (10 mg, 0.008 mmol) and heated at 90° C. overnight. The reaction mixture was purified by column chromatography. The foregoing compound was treated with TFA-DCM (1:1, 2 mL), evaporated in vacuo and purified by ion-exchange chromatography (Isolute® SCX-2 cartridge, eluting with NH3 in methanol) and preparative TLC to give the title compound (6.5 mg, 10%).

Workup

  1. customThe reaction mixture was purified by column chromatography
  2. additionThe foregoing compound was treated with TFA-DCM (1:1, 2 mL)
  3. customevaporated in vacuo
  4. custompurified by ion-exchange chromatography (Isolute® SCX-2 cartridge, eluting with NH3 in methanol) and preparative TLC

Sources & evidence

ORD record
ord-cb342a856060461d891b533f69179ecd
Source dataset
uspto-grants-2014_04
Patent number
US08697693B2

Reaction notes

Loading…