2-[4-(4-Morpholin-4-yl-2-(tributylstannanyl)-thieno[3,2-d]pyrimidin-6-ylmethyl)piperazin-1-yl]isobutyramide → HCID 59605699, compound

HRID 1945756Notes

Reaction equation

HRID 1945756 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[C:48]2[CH:49]=[CH:50][NH:51][C:47]=2[CH:46]=[C:45]([CH3:52])[N:44]=1>O1CCOCC1.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.S1C=CC=C1C([O-])=O.[Cu+]>[CH3:40][C:36]([N:33]1[CH2:32][CH2:31][N:30]([CH2:29][C:27]2[S:28][C:8]3[C:7]([N:1]4[CH2:2][CH2:3][O:4][CH2:5][CH2:6]4)=[N:12][C:11]([C:43]4[C:48]5[CH:49]=[CH:50][NH:51][C:47]=5[CH:46]=[C:45]([CH3:52])[N:44]=4)=[N:10][C:9]=3[CH:26]=2)[CH2:35][CH2:34]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 596053264-Bromo-6-methyl-1H-pyrrolo[3,2-c]pyridine

Product 1

HCID 59605699HCID 59605699, compoundYield 22.9%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
150 °C

Procedure

A mixture of 2-[4-(4-morpholin-4-yl-2-(tributylstannanyl)thieno[3,2-d]pyrimidin-6-ylmethyl)-piperazin-1-yl]isobutyramide (100 mg, 0.14 mmol), 4-bromo-6-methyl-1H-pyrrolo[3,2-c]pyridine (20 mg, 0.09 mmol), tetrakis(triphenylphosphine)palladium (17 mg, 10 mol %) and copper(I)-thiophene-2-carboxylate (6 mg, 20 mol %) in dioxane (1.5 mL) was purged with argon gas then heated at 150° C., for 20 min, in a microwave reactor. The cooled reaction mixture was loaded onto an Isolute® SCX-2 cartridge, washed with MeOH/DCM then eluted with 2 M NH3 in MeOH/DCM. The resulting residue was purified by column chromatography (Si—PPC, 2 M NH3 in MeOH:DCM, gradient 0:100 to 10:90) followed by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 20 mM triethylamine in water on a gradient of acetonitrile 90:10 to 02:98) to give 170 as an off-white solid (11 mg, 22%). LCMS RT 5.14 min, [M+H]+ 535. 1H NMR (CDCl3, 400 MHz) δ 7.41 (s, 1 H), 7.29-7.25 (m, 2 H), 7.14 (s, 1 H), 7.09 (d, J=5.3 Hz, 1 H), 5.36 (d, J=5.3 Hz, 1 H), 4.07 (t, J=4.6 Hz, 4 H), 3.88 (t, J=4.6 Hz, 4 H), 3.83 (s, 2 H), 2.70 (s, 3 H), 2.58 (m, 8 H), 1.23 (s, 6 H)

Workup

  1. customwas purged with argon gas
  2. customThe cooled reaction mixture
  3. washwashed with MeOH/DCM
  4. washthen eluted with 2 M NH3 in MeOH/DCM
  5. customThe resulting residue was purified by column chromatography (Si—PPC, 2 M NH3 in MeOH:DCM, gradient 0:100 to 10:90)

Sources & evidence

ORD record
ord-79ecc2ad4fe94635a1c5265333f87cc0
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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