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

HRID 1692893Notes

Reaction equation

HRID 1692893 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.C(OC([N:49]1[C:53]2=[CH:54][N:55]=[CH:56][CH:57]=[C:52]2[C:51](Br)=[CH:50]1)=O)(C)(C)C>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.O1CCOCC1>[CH3:41][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[CH2:6][CH2:5][O:4][CH2:3][CH2:2]4)=[N:12][C:11]([C:51]4[C:52]5[C:53](=[CH:54][N:55]=[CH:56][CH:57]=5)[NH:49][CH:50]=4)=[N:10][C:9]=3[CH:26]=2)[CH2:35][CH2:34]1)([CH3:40])[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 59603463tert-butyl 3-bromo-1H-pyrrolo[2,3-c]pyridine-1-carboxylate

Product 1

HCID 596034302-methyl-2-(4-((4-morpholino-2-(1H-pyrrolo[2,3-c]pyridin-3-yl)thieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)propanamideYield 10%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
140 °C

Procedure

To a mixture of 2-[4-(4-morpholin-4-yl-2-tributylstannanyl-thieno[3,2-d]pyrimidin-6-ylmethyl)-piperazin-1-yl]-isobutyramide (275 mg, 0.396 mmol), 3-bromo-pyrrolo[2,3-c]pyridine-1-carboxylic acid tert-butyl ester (177 mg, 0.596 mmol), copper(I) thiophene-2-carboxylate (76 mg, 0.40 mmol), and Pd(PPh3)4 (46 mg, 0.040 mmol) was added 1,4-dioxane (2 mL). The reaction vessel was evacuated and back filled with argon under sonication. The reaction mixture was heated in the microwave at 140° C. for 20 minutes. The reaction mixture volume was doubled with a solution of 10% MeOH in DCM. The mixture was filtered through a plug of solka floc and the filtrate was concentrated. The green residue was triturated with hexane and dried in vacuo. The light green solid was purified by flash chromatography (silica, 0-10% of a 9:1 MeOH/NH4OH solution in DCM) to give 137 (20.6 mg, 10%) as an off-white solid. LCMS: M+H+=521. 1H-NMR (300 MHz, DMSO-d6): δ 12.0 (s, 1H), 8.79 (s, 1), 8.39 (d, 1H), 8.37 (d, 1H), 8.23 (d, 1H), 7.35 (s, 1H), 7.07 (d, 1H), 6.95 (d, 1H), 3.97 (m, 4H), 3.83 (m, 6), 2.55 (m, 4H), 2.46 (m, 4H), 1.08 (s, 6H)

Workup

  1. customThe reaction vessel was evacuated
  2. additionback filled with argon under sonication
  3. filtrationThe mixture was filtered through a plug of solka floc
  4. concentrationthe filtrate was concentrated
  5. customThe green residue was triturated with hexane
  6. customdried in vacuo
  7. customThe light green solid was purified by flash chromatography (silica, 0-10% of a 9:1 MeOH/NH4OH solution in DCM)

Sources & evidence

ORD record
ord-20a3975404b246db8d9bd05ea23a1129
Source dataset
uspto-grants-2012_04
Patent number
US08158625B2

Reaction notes

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