HCID 57506731, 화합물 → HCID 67492555, 화합물

HRID 1922930노트

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HRID 1922930 반응식
[N:1]1([C:7]2[C:8]3[N: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)[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.[C:42]1([S:48]([N:51]2[C:59]3[CH:58]=[CH:57][N:56]=[C:55](Br)[C:54]=3[CH:53]=[CH:52]2)(=[O:50])=[O:49])[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1>O1CCOCC1.S1C=CC=C1C([O-])=O.[Cu+]>[C:42]1([S:48]([N:51]2[C:59]3[CH:58]=[CH:57][N:56]=[C:55]([C:11]4[N:12]=[C:7]([N:1]5[CH2:6][CH2:5][O:4][CH2:3][CH2:2]5)[C:8]5[N:28]=[C:27]([CH2:29][N:30]6[CH2:35][CH2:34][N:33]([C:36]([CH3:40])([CH3:41])[C:37]([NH2:39])=[O:38])[CH2:32][CH2:31]6)[S:26][C:9]=5[N:10]=4)[C:54]=3[CH:53]=[CH:52]2)(=[O:50])=[O:49])[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=1

참가 물질

5

반응물 2

HCID 57506731HCID 57506731, 화합물HCID 596034392-[4-(7-Morpholin-4-yl-5-(tributylstannanyl)thiazolo[5,4-d]pyrimidin-2-ylmethyl)piperazin-1-yl]isobutyramide

생성물 1

HCID 67492555HCID 67492555, 화합물

시약·촉매·용매 2

HCID 11194830Cuprous 2-thiophenecarboxylate촉매HCID 312751,4-Dioxane용매

실험 절차

A degassed solution of 2-[4-(7-morpholin-4-yl-5-(tributylstannanyl)thiazolo[5,4-d]pyrimidin-2-ylmethyl)piperazin-1-yl]isobutyramide (250 mg, 0.36 mmol), 1-benzenesulfonyl-4-bromo-1H-pyrrolo[3,2-c]pyridine (130 mg, 0.39 mmol), PdCl2{PtBu2(Ph-p-Nme2)}2 (26 mg, 0.036 mmol) and copper(I) thiophene-2-carboxylate (14 mg, 0.07 mmol) in 1,4-dioxane (4 mL) was subjected to microwave irradiation at 140° C. for 20 minutes. The reaction mixture was cooled to ambient temperature and loaded onto an Isolute® SCX-2 cartridge (10 g). The cartridge was then washed with MeOH and the desired product was subsequently eluted using 2 M NH3 in MeOH. The product was collected and concentrated to give 2-{4-[5-(1-benzenesulfonyl-1H-pyrrolo[3,2-c]pyridin-4-yl)-7-morpholin-4-ylthiazolo[5,4-d]pyrimidin-2-ylmethyl]piperazin-1-yl}isobutyramide as a crude oil. Aqueous NaOH (12.5 M, 0 4 mL) was added to a solution of 2-{4-[5-(1-benzenesulfonyl-1H-pyrrolo[3,2-c]pyridin-4-yl)-7-morpholin-4-yl-thiazolo[5,4-d]pyrimidin-2-ylmethyl]-piperazin-1-yl}isobutyramide in 1,4-dioxane (4 mL) and IMS (4 mL). The reaction mixture was stirred at ambient temperature for 45 min, then concentrated in vacuo. The residue was dissolved in MeOH then loaded onto an Isolute® SCX-2 cartridge (10 g). The cartridge was then washed with MeOH and the desired product was subsequently eluted using 2 M NH3 in MeOH. The product was collected and concentrated to afford a solid. The solid was purified by flash chromatography (Si—PPC, DCM:MeOH, 100:0 to 98:2 to 96:4) followed by reversed phase HPLC (Phenomenex Luna C-18, 20 mM Et3N in water on a gradient of 20 mM Et3N in acetonitrile 95:5 to 2:98) to afford 169 as a yellow solid (43 mg, 23%). LCMS (method E): RT=5.03 min, [M+H]+=522.2. 1H NMR (CDCl3, 400 MHz) δ 8.55 (d, J=5.6 Hz, 1 H), 7.45-7.40 (m, 2 H), 7.38 (d, J=3.3 Hz, 1 H), 7.11 (d, J=5.3 Hz, 1 H), 5.25 (d, J=5.3 Hz, 1 H), 4.53-4.42 (m, 4 H), 3.90 (m, 6 H), 2.68 (m, 4 H), 2.62 (m, 4 H), 1.25 (s, 6 H)

후처리

  1. customirradiation at 140° C. for 20 minutes
  2. washThe cartridge was then washed with MeOH
  3. washthe desired product was subsequently eluted
  4. customThe product was collected
  5. concentrationconcentrated

출처 및 근거

ORD 기록
ord-fcb7f731b3eb41799bfef142e9494f1d
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08173650B2

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