2-[4-(4-Morpholin-4-yl-2-(tributylstannanyl)-thieno[3,2-d]pyrimidin-6-ylmethyl)piperazin-1-yl]isobutyramide → 2-Methyl-2-(4-((2-(8-methylimidazo[1,2-a]pyridin-5-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)propanamide

HRID 1945780

反応式

HRID 1945780 の反応式
[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[N:48]2[CH:49]=[CH:50][N:51]=[C:47]2[C:46]([CH3:52])=[CH:45][CH: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+]>[CH3:41][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[CH2:2][CH2:3][O:4][CH2:5][CH2:6]4)=[N:12][C:11]([C:43]4[N:48]5[CH:49]=[CH:50][N:51]=[C:47]5[C:46]([CH3:52])=[CH:45][CH:44]=4)=[N:10][C:9]=3[CH:26]=2)[CH2:31][CH2:32]1)([CH3:40])[C:37]([NH2:39])=[O:38]

参加物

6

反応物 2

HCID 575067302-[4-(4-Morpholin-4-yl-2-(tributylstannanyl)-thieno[3,2-d]pyrimidin-6-ylmethyl)piperazin-1-yl]isobutyramideHCID 596052165-Bromo-8-methylimidazo[1,2-a]pyridine

生成物 1

HCID 596059892-Methyl-2-(4-((2-(8-methylimidazo[1,2-a]pyridin-5-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)propanamide収率 62%

試薬・触媒・溶媒 3

HCID 11194830Cuprous 2-thiophenecarboxylate触媒HCID 178418397HCID 178418397、化合物触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
150 °C

実験手順

A mixture of 2-[4-(4-morpholin-4-yl-2-(tributylstannanyl)-thieno[3,2-d]pyrimidin-6-ylmethyl)piperazin-1-yl]isobutyramide (205 mg, 0.30 mmol), 5-bromo-8-methylimidazo[1,2-a]pyridine (75 mg, 0.35 mmol), Pd(PPh3)4 (34 mg, 0.03 mmol) and copper(I) thiophene-2-carboxylate (11 mg, 0.06 mmol) in dioxane (3 mL) was purged with argon gas then heated at 150° C., for 20 min, in a microwave reactor. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge (10 g). The cartridge was washed with MeOH then the desired product was eluted with 2 M NH3 in MeOH. The resulting residue was purified by flash chromatography (Si—PPC, MeOH:DCM, gradient 0:100 to 10:90) to give a solid that was triturated in MeOH, filtered and dried at 60° C. under vacuum for 24 hours to give 201 as a white solid (97 mg, 62%). LCMS (Method G) RT 5.11 min; [M+H]+ 535. 1H NMR (400 MHz, CHCl3-d): δ 9.29 (s, 1 H); 7.93 (d, J=7.3 Hz, 1 H); 7.75 (s, 1 H); 7.37 (s, 1 H); 7.15 (d, J=7.3 Hz, 1 H); 7.13-6.96 (m, 1 H); 5.21 (s, 1 H); 4.06 (t, J=4.7 Hz, 4 H); 3.91 (t, J=4.7 Hz, 4 H); 3.86 (s, 2 H); 2.73 (s, 3 H); 2.62 (s, 8 H); 1.25 (s, 6 H)

後処理

  1. customwas purged with argon gas
  2. washThe cartridge was washed with MeOH
  3. washthe desired product was eluted with 2 M NH3 in MeOH
  4. customThe resulting residue was purified by flash chromatography (Si—PPC, MeOH:DCM, gradient 0:100 to 10:90)
  5. customto give a solid
  6. customthat was triturated in MeOH
  7. filtrationfiltered
  8. customdried at 60° C. under vacuum for 24 hours

出典と根拠

ORDレコード
ord-cbabc9c2c2354bd5865fd5644fe4907f
出典データセット
uspto-grants-2013_03
特許番号
US08394796B2

関連ノート

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