Sodium Hydroxide → 2-(4-((2-(2-Fluorobenzofuran-3-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)-2-methylpropanamide

HRID 1945750Notes

Reaction equation

HRID 1945750 reaction equation
[CH3:1][C:2]([N:7]1[CH2:12][CH2:11][N:10]([CH2:13][C:14]2[S:22][C:21]3[C:20]([N:23]4[CH2:28][CH2:27][O:26][CH2:25][CH2:24]4)=[N:19][C:18]([Sn](CCCC)(CCCC)CCCC)=[N:17][C:16]=3[CH:15]=2)[CH2:9][CH2:8]1)([CH3:6])[C:3]([NH2:5])=[O:4].Br[C:43]1[C:47]2[CH:48]=[CH:49][CH:50]=[CH:51][C:46]=2[O:45][C:44]=1[F:52].[OH-].[Na+]>O1CCOCC1.C(O)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>[F:52][C:44]1[O:45][C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][C:47]=2[C:43]=1[C:18]1[N:19]=[C:20]([N:23]2[CH2:24][CH2:25][O:26][CH2:27][CH2:28]2)[C:21]2[S:22][C:14]([CH2:13][N:10]3[CH2:9][CH2:8][N:7]([C:2]([CH3:6])([CH3:1])[C:3]([NH2:5])=[O:4])[CH2:12][CH2:11]3)=[CH:15][C:16]=2[N:17]=1

Participants

8

Reactant 3

HCID 14798Sodium HydroxideHCID 575067302-[4-(4-Morpholin-4-yl-2-(tributylstannanyl)-thieno[3,2-d]pyrimidin-6-ylmethyl)piperazin-1-yl]isobutyramideHCID 674926943-Bromo-2-fluorobenzofuran

Product 1

HCID 498347552-(4-((2-(2-Fluorobenzofuran-3-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)-2-methylpropanamide

Reagents, catalysts & solvents 4

HCID 11194830Cuprous 2-thiophenecarboxylateCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
65 °C

Procedure

To a degassed mixture of 2-methyl-2-(4-((4-morpholino-2-(tributylstannyl)thieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)propanamide (150 mg, 0.22 mmol), 3-bromo-2-fluorobenzofuran (0.22 mmol), copper(I) thiophene-2-carboxylate (41 mg, 0.22 mmol) in dioxane (2 mL) was added Pd(PPh3)4 (12 mg, 0.011 mmol). The reaction mixture was reacted in the microwave at 140° C. for 35 min. The reaction mixture was filtered through paper and concentrated. The crude product was purified by flash chromatography (20% MeOH in DCM) to give a yellow paste which was dissolved in dioxane (5 mL) and ethanol (1 mL). A 12 M aqueous solution of NaOH was then added. The resulting mixture was then stirred at 65° C. for 15 hours. The reaction mixture was then loaded onto a Biotage Isolute SPE SCX-2 column. The column was washed with MeOH and the desired product was then eluted with 2 M NH3 in MeOH and further purified by RP-HPLC to give 163. LCMS: M+H+=539.2. 1H-NMR (400 MHz, DMSO-d6): δ 8.46 (d, 1H), 7.63 (d, 1H), 7.41 (m, 3H), 7.05 (d, 1H), 6.93 (d, 1H), 3.97 (m, 4H), 3.86 (s, 2H), 3.82 (m, 4H), 2.31-2.62 (m, 8H), 1.08 (s, 6H)

Workup

  1. customThe reaction mixture was reacted in the microwave at 140° C. for 35 min
  2. filtrationThe reaction mixture was filtered through paper
  3. concentrationconcentrated
  4. customThe crude product was purified by flash chromatography (20% MeOH in DCM)
  5. customto give a yellow paste which
  6. washThe column was washed with MeOH
  7. washthe desired product was then eluted with 2 M NH3 in MeOH
  8. customfurther purified by RP-HPLC

Sources & evidence

ORD record
ord-14ad408b3d6943e8a67148df072abf4c
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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