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Cesium carbonate → 4-(5-(2-Methylbenzofuran-3-yl)-2-((3-morpholinoazetidin-1-yl)methyl)thiazolo[5,4-d]pyrimidin-7-yl)morpholine

HRID 1922971
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HRID 1922971 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[CH2:15][CH:14]([N:16]4[CH2:21][CH2:20][O:19][CH2:18][CH2:17]4)[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.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>[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[CH2:15][CH:14]([N:16]4[CH2:21][CH2:20][O:19][CH2:18][CH2:17]4)[CH2:13]3)[S:8][C:6]=2[N:7]=1
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참가 물질

7

반응물 3

HCID 10796Cesium carbonateHCID 596034604-(5-Chloro-2-((3-morpholinoazetidin-1-yl)methyl)thiazolo[5,4-d]pyrimidin-7-yl)morpholineHCID 673417654,4,5,5-Tetramethyl-2-(2-methylbenzofuran-3-yl)-1,3,2-dioxaborolane

생성물 1

HCID 498322774-(5-(2-Methylbenzofuran-3-yl)-2-((3-morpholinoazetidin-1-yl)methyl)thiazolo[5,4-d]pyrimidin-7-yl)morpholine수율 48%

시약·촉매·용매 3

HCID 178418397
HCID 178418397, 화합물
촉매
HCID 962Water용매
HCID 312751,4-Dioxane용매

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온도
140 °C

실험 절차

A mixture of 5-chloro-7-morpholin-4-yl-2-(3-morpholin-4-ylazetidin-1-ylmethyl)thiazolo[5,4-d]pyrimidine (100 mg, 0.24 mmol), 2-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)benzofuran (94 mg, 0.37 mmol), tetrakis(triphenylphosphine)palladium (28 mg, 0.02 mmol) and Cs2CO3 (159 mg, 0.48 mmol) in dioxane (6 mL) and H2O (3 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, MeOH:EtOAc, 0-5%) to afford 212 as a cream solid (58 mg, 48%). LCMS (Method G): RT 9.83 min, [M+H]+ 507.3. 1H NMR (CDCl3, 400 MHz): δ 8.39-8.36 (m, 1 H); 7.45-7.42 (m, 1 H); 7.32-7.24 (m, 2 H); 4.40 (m, 4 H); 4.01 (s, 2 H); 3.89 (m, 4 H); 3.70 (m, 6 H); 3.18-3.08 (m, 3 H); 2.92 (s, 3H) and 2.36 (m, 4 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, MeOH:EtOAc, 0-5%)

출처 및 근거

ORD 기록
ord-fa208adc6cfe45c68e9a9f2867e5e020
출처 데이터셋
uspto-grants-2012_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08173650B2

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