5-Bromoimidazo(1,2-a)pyridine → 4-(5-(Imidazo[1,2-a]pyridin-5-yl)-2-((3-morpholinoazetidin-1-yl)methyl)thiazolo[5,4-d]pyrimidin-7-yl)morpholine

HRID 1923309

반응식

HRID 1923309 반응식
[N:1]1([C:7]2[C:8]3[N:28]=[C:27]([CH2:29][N:30]4[CH2:33][CH:32]([N:34]5[CH2:39][CH2:38][O:37][CH2:36][CH2:35]5)[CH2:31]4)[S: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:41]1[N:46]2[CH:47]=[CH:48][N:49]=[C:45]2[CH:44]=[CH:43][CH:42]=1>O1CCOCC1.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>[N:49]1[CH:48]=[CH:47][N:46]2[C:41]([C:11]3[N:12]=[C:7]([N:1]4[CH2:2][CH2:3][O:4][CH2:5][CH2:6]4)[C:8]4[N:28]=[C:27]([CH2:29][N:30]5[CH2:31][CH:32]([N:34]6[CH2:39][CH2:38][O:37][CH2:36][CH2:35]6)[CH2:33]5)[S:26][C:9]=4[N:10]=3)=[CH:42][CH:43]=[CH:44][C:45]=12

참가 물질

6

반응물 2

HCID 130372415-Bromoimidazo(1,2-a)pyridineHCID 596060507-Morpholin-4-yl-2-(3-morpholin-4-ylazetidin-1-ylmethyl)-5-(tributylstannanyl)thiazolo[5,4-d]pyrimidine

생성물 1

HCID 498334764-(5-(Imidazo[1,2-a]pyridin-5-yl)-2-((3-morpholinoazetidin-1-yl)methyl)thiazolo[5,4-d]pyrimidin-7-yl)morpholine수율 55.4%

시약·촉매·용매 3

HCID 11194830Cuprous 2-thiophenecarboxylate촉매HCID 178418397HCID 178418397, 화합물촉매HCID 312751,4-Dioxane용매

실험 절차

A mixture of 7-morpholin-4-yl-2-(3-morpholin-4-ylazetidin-1-ylmethyl)-5-(tributylstannanyl)thiazolo[5,4-d]pyrimidine (0.25 g, 0.37 mmol), 5-bromoimidazo[1,2-a]pyridine (0.082 g, 0.41 mmol), copper(I) 2-thiophene carboxylate (0.015 g, 0.075 mmol) and Pd(PPh3)4 (0.044 g, 0.037 mmol) in dioxane (3 mL) was subjected to microwave irradiation at 150° C. for 60 min. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH and the desired product was eluted using 2 M NH3 in MeOH. The eluent was concentrated in vacuo and the residue was purified by flash chromatography (Si—PPC, MEOH:DCM, 0:100 to 10:90) followed by reverse phase HPLC (Phenomenex Gemini 5u C18, 20 mM triethylamine in water on a gradient of acetonitrile 95:5 to 2:98) to give 700 as a yellow solid (0.101 g, 55%). LCMS (Method E): RT=3.98 min, [M+H]+ 493.15. 1H NMR (CDCl3, 400 MHz) δ 9.16 (s, 1 H); 7.98 (dd, J=7.2, 1.2 Hz, 1 H); 7.81 (d, J=8.9 Hz, 1 H); 7.76 (d, J=1.2 Hz, 1 H); 7.33 (dd, J=8.9, 7.2 Hz, 1 H); 4.47-4.32 (m, 4 H); 4.04 (s, 2 H); 3.89 (t, J=4.6 Hz, 4 H); 3.74 (t, J=4.6 Hz, 4 H); 3.69 (t, J=6.4 Hz, 2 H); 3.23-3.15 (m, 2 H); 3.14 (t, J=6.4 Hz, 1 H); 2.40-2.36 (m, 4 H)

후처리

  1. customirradiation at 150° C. for 60 min
  2. washThe cartridge was washed with MeOH
  3. washthe desired product was eluted
  4. concentrationThe eluent was concentrated in vacuo
  5. customthe residue was purified by flash chromatography (Si—PPC, MEOH:DCM, 0:100 to 10:90)

출처 및 근거

ORD 기록
ord-78d1b4cdbec24477aed08e97b1be391d
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08173650B2

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