2-[4-(4-Morpholin-4-yl-2-(tributylstannanyl)-thieno[3,2-d]pyrimidin-6-ylmethyl)piperazin-1-yl]isobutyramide → 2-methyl-2-(4-((2-(7-methyl-1H-pyrrolo[2,3-c]pyridin-4-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)propanamide

HRID 1945723Notes

Reaction equation

HRID 1945723 reaction equation
[N:1]1([C:7]2[C:8]3[S:28][C:27]([CH2:29][N:30]4[CH2:35][CH2:34][N:33]([C:36]([CH3:41])([CH3:40])[C:37]([NH2:39])=[O:38])[CH2:32][CH2:31]4)=[CH:26][C:9]=3[N:10]=[C:11]([Sn](CCCC)(CCCC)CCCC)[N:12]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Br[C:43]1[CH:48]=[N:47][C:46]([CH3:49])=[C:45]2[NH:50][CH:51]=[CH:52][C:44]=12>O1CCOCC1.S1C=CC=C1C([O-])=O.[Cu+].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>[CH3:40][C:36]([N:33]1[CH2:34][CH2:35][N:30]([CH2:29][C:27]2[S:28][C:8]3[C:7]([N:1]4[CH2:6][CH2:5][O:4][CH2:3][CH2:2]4)=[N:12][C:11]([C:43]4[CH:48]=[N:47][C:46]([CH3:49])=[C:45]5[NH:50][CH:51]=[CH:52][C:44]=45)=[N:10][C:9]=3[CH:26]=2)[CH2:31][CH2:32]1)([CH3:41])[C:37]([NH2:39])=[O:38]

Participants

6

Reactant 2

HCID 575067302-[4-(4-Morpholin-4-yl-2-(tributylstannanyl)-thieno[3,2-d]pyrimidin-6-ylmethyl)piperazin-1-yl]isobutyramideHCID 596816194-bromo-7-methyl-1H-pyrrolo[2,3-c]pyridine

Product 1

HCID 596052952-methyl-2-(4-((2-(7-methyl-1H-pyrrolo[2,3-c]pyridin-4-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)propanamideYield 46.8%

Reagents, catalysts & solvents 3

HCID 11194830Cuprous 2-thiophenecarboxylateCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 2-[4-(4-morpholin-4-yl-2-(tributylstannanyl)thieno[3,2-d]pyrimidin-6-ylmethyl)-piperazin-1-yl]isobutyramide (197 mg, 0.28 mmol), 4-bromo-7-methyl-1H-pyrrolo[2,3-c]pyridine (60 mg, 0.28 mmol), copper(I) 2-thiophene carboxylate (11 mg, 0.056 mmol), and Pd(PPh3)4 (32 mg, 0.028 mmol) in dioxane (3 mL) was placed in a microwave tube which was sealed and evacuated. The reaction vessel was degassed and purged with argon (×3). The reaction mixture was irradiated at 140° C. for 20 min. The cooled mixture was then poured onto an Isolute® SCX-II cartridge and the cartridge was washed with MeOH (100 mL). The product was eluted with 2 M NH3 in MeOH. The pooled fractions were evaporated and the product was further purified by chromatography on silica (Si—PPC), using MeOH in DCM (0-10%) as eluent. The pooled product-containing fractions were evaporated and the residue was crystallized from hot EtOAc to afford 132 as a white crystalline solid (70 mg, 46%). LCMS: (Method F): RT 5.02 min; [M+H]+ 535.2. 1H NMR (DMSO, 400 MHz): δ 11.71 (s, 1 H); 9.02 (s, 1 H); 7.66 (t, J=2.7 Hz, 1 H); 7.44 (s, 1 H); 7.38 (dd, J=2.9, 1.9 Hz, 1 H); 7.08 (d, J=3.5 Hz, 1 H); 6.95 (d, J=3.5 Hz, 1 H); 3.99 (t, J=4.6 Hz, 4 H); 3.86 (s, 2 H); 3.85-3.80 (m, 4 H); 2.73 (s, 3 H); 2.62-2.53 (m, 4 H); 2.47 (s, 4 H); 1.08 (s, 6 H)

Workup

  1. customwas placed in a microwave tube
  2. customwhich was sealed
  3. customevacuated
  4. customThe reaction vessel was degassed
  5. custompurged with argon (×3)
  6. customThe reaction mixture was irradiated at 140° C. for 20 min
  7. additionThe cooled mixture was then poured onto an Isolute® SCX-II cartridge
  8. washthe cartridge was washed with MeOH (100 mL)
  9. washThe product was eluted with 2 M NH3 in MeOH
  10. customThe pooled fractions were evaporated
  11. customthe product was further purified by chromatography on silica (Si—PPC)
  12. additionThe pooled product-containing fractions
  13. customwere evaporated
  14. customthe residue was crystallized from hot EtOAc

Sources & evidence

ORD record
ord-7b245c34e4fd4502a736c5f39fddc16d
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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