Sodium Hydroxide → HCID 49818908, compound

HRID 1692890Notes

Reaction equation

HRID 1692890 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:51]2[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=2)[N:45](S(C2C=CC=CC=2)(=O)=O)[C:44]=1[CH2:61][O:62][CH3:63].[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>[CH3:63][O:62][CH2:61][C:44]1[NH:45][C:46]2[C:51]([C:43]=1[C:18]1[N:19]=[C:20]([N:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)[C:21]3[S:22][C:14]([CH2:13][N:10]4[CH2:11][CH2:12][N:7]([C:2]([CH3:6])([CH3:1])[C:3]([NH2:5])=[O:4])[CH2:8][CH2:9]4)=[CH:15][C:16]=3[N:17]=1)=[CH:50][CH:49]=[CH:48][CH:47]=2

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 67280780HCID 67280780, compound

Product 1

HCID 49818908HCID 49818908, compoundYield 10.2%

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-(methoxymethyl)-1-(phenylsulfonyl)-1H-indole (82 mg, 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 126 (12.4 mg, 10.2%). LCMS: M+H+=564.3. 1H-NMR (400 MHz, DMSO-d6): δ 11.48 (s, 1H), 8.55 (m, 1H), 7.44 (m, 1H), 7.35 (s, 1H), 7.10 (m, 2H), 7.05 (m, 1H), 6.93 (m, 1H), 5.19 (s, 2H), 3.90 (m, 4H), 3.83 (m, 6H), 3.47 (s, 3H), 2.42-2.58 (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-67eb79cc4f7e4bb38195d2c9ccef2d06
Source dataset
uspto-grants-2012_04
Patent number
US08158625B2

Reaction notes

Loading…