4-Bromo-1H-pyrrolo(2,3-c)pyridine → 4-(1-((7-morpholino-5-(1H-pyrrolo[2,3-c]pyridin-4-yl)thiazolo[5,4-d]pyrimidin-2-yl)methyl)azetidin-3-yl)morpholine

HRID 1922929

反応式

HRID 1922929 の反応式
[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[CH:46]=[N:45][CH:44]=[C:43]2[NH:47][CH:48]=[CH:49][C:42]=12>O1CCOCC1.S1C=CC=C1C([O-])=O.[Cu+]>[O:4]1[CH2:3][CH2:2][N:1]([C:7]2[C:8]3[N:28]=[C:27]([CH2:29][N:30]4[CH2:31][CH:32]([N:34]5[CH2:35][CH2:36][O:37][CH2:38][CH2:39]5)[CH2:33]4)[S:26][C:9]=3[N:10]=[C:11]([C:41]3[CH:46]=[N:45][CH:44]=[C:43]4[NH:47][CH:48]=[CH:49][C:42]=34)[N:12]=2)[CH2:6][CH2:5]1

参加物

5

反応物 2

HCID 125100554-Bromo-1H-pyrrolo(2,3-c)pyridineHCID 596060507-Morpholin-4-yl-2-(3-morpholin-4-ylazetidin-1-ylmethyl)-5-(tributylstannanyl)thiazolo[5,4-d]pyrimidine

生成物 1

HCID 596058854-(1-((7-morpholino-5-(1H-pyrrolo[2,3-c]pyridin-4-yl)thiazolo[5,4-d]pyrimidin-2-yl)methyl)azetidin-3-yl)morpholine収率 14%

試薬・触媒・溶媒 2

HCID 11194830Cuprous 2-thiophenecarboxylate触媒HCID 312751,4-Dioxane溶媒

実験手順

A degassed solution of 7-morpholin-4-yl-2-(3-morpholin-4-yl-azetidin-1-ylmethyl)-5-(tributylstannanyl)thiazolo[5,4-d]pyrimidine (120 mg, 0.18 mmol), 4-bromo-1H-pyrrolo[2,3-c]pyridine (46 mg, 0.23 mmol), PdCl2{PtBu2(Ph-p-Nme2)}2 (13 mg, 0.018 mmol) and copper(I) thiophene-2-carboxylate (7 mg, 0.036 mmol) in 1,4-dioxane (2.5 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 a yellow oil. The oil was purified by chromatography (Si—PPC, DCM:MeOH, 100:0 to 98:2 to 95:5) to afford 168 as a yellow solid (12 mg, 14%). LCMS (Method E): RT=4.15 min, [M+H]− 493.2. 1H NMR (CDCl3, 400 MHz) δ 9.28 (bs, 1 H), 8.90 (s, 1 H), 7.53 (m, 2 H), 4.45 (m, 4 H), 4.02 (s, 2H), 3.90 (t, J=4.7 Hz, 4 H), 3.76-3.65 (m, 6 H), 3.19-3.09 (m, 3 H), 2.36 (d, J=4.76 Hz, 4H).

後処理

  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
  6. customto give a yellow oil
  7. customThe oil was purified by chromatography (Si—PPC, DCM:MeOH, 100:0 to 98:2 to 95:5)

出典と根拠

ORDレコード
ord-6da01e0229234ad289d405a53a05e7f8
出典データセット
uspto-grants-2012_05
特許番号
US08173650B2

関連ノート

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