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Cesium carbonate → 2-(1-((5-(2-Methylbenzofuran-3-yl)-7-morpholinothiazolo[5,4-d]pyrimidin-2-yl)methyl)piperidin-4-yl)propan-2-ol

HRID 1945788
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HRID 1945788 반응식
Cl[C:2]1[N:3]=[C:4]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[C:5]2[N:10]=[C:9]([CH2:11][N:12]3[CH2:17][CH2:16][CH:15]([C:18]([OH:21])([CH3:20])[CH3:19])[CH2:14][CH2:13]3)[S:8][C:6]=2[N:7]=1.[CH3:28][C:29]1[O:30][C:31]2[CH:46]=[CH:45][CH:44]=[CH:43][C:32]=2[C:33]=1B1OC(C)(C)C(C)(C)O1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:28][C:29]1[O:30][C:31]2[CH:46]=[CH:45][CH:44]=[CH:43][C:32]=2[C:33]=1[C:2]1[N:3]=[C:4]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[C:5]2[N:10]=[C:9]([CH2:11][N:12]3[CH2:17][CH2:16][CH:15]([C:18]([OH:21])([CH3:20])[CH3:19])[CH2:14][CH2:13]3)[S:8][C:6]=2[N:7]=1
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참가 물질

7

반응물 3

HCID 10796Cesium carbonateHCID 596055142-(1-((5-Chloro-7-morpholinothiazolo[5,4-d]pyrimidin-2-yl)methyl)piperidin-4-yl)propan-2-olHCID 673417654,4,5,5-Tetramethyl-2-(2-methylbenzofuran-3-yl)-1,3,2-dioxaborolane

생성물 1

HCID 498322752-(1-((5-(2-Methylbenzofuran-3-yl)-7-morpholinothiazolo[5,4-d]pyrimidin-2-yl)methyl)piperidin-4-yl)propan-2-ol수율 48%

시약·촉매·용매 3

HCID 11979704
Tetrakis(triphenylphosphine)palladium
촉매
HCID 962Water용매
HCID 312751,4-Dioxane용매

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온도
140 °C

실험 절차

A mixture of 2-[1-(5-chloro-7-morpholin-4-ylthiazolo[5,4-d]pyrimidin-2-ylmethyl)-piperidin-4-yl]propan-2-ol (50 mg, 0.12 mmol), 2-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)benzofuran (47 mg, 0.18 mmol), tetrakis(triphenylphosphine) palladium (14 mg, 0.01 mmol) and Cs2CO3 (80 mg, 0.24 mmol) in dioxane (3 mL) and H2O (1.5 mL) was purged with argon then heated at 140° C. for 30 min in a microwave reactor. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge which was washed with DCM/MeOH and the product eluted with 2M NH3/MeOH. The resulting residue was purified by column chromatography (Si—PCC, EtOAc:cyclohexane, 0-90%) to afford 210 as a white solid (29 mg, 48%). LCMS (Method G): RT 10.16 min, [M+H]+ 508.4. 1H NMR (CDCl3, 400 MHz): δ 8.40-8.37 (m, 1 H); 7.45-7.40 (m, 1 H); 7.32-7.24 (m, 2 H); 4.40 (m, 4 H); 3.94-3.84 (m, 6 H); 3.11 (m, 2 H); 2.92 (s, 3 H); 2.21 (m, 2 H); 1.78 (m, 2 H); 1.48 (m, 2 H) and 1.21 (m, 7 H)

후처리

  1. customwas purged with argon
  2. washwas washed with DCM/MeOH
  3. washthe product eluted with 2M NH3/MeOH
  4. customThe resulting residue was purified by column chromatography (Si—PCC, EtOAc:cyclohexane, 0-90%)

출처 및 근거

ORD 기록
ord-9a140649ea5d429fb890be406a1085bf
출처 데이터셋
uspto-grants-2013_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08394796B2

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