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Cesium carbonate → 4-(1-((2-(2-Methylbenzofuran-3-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)azetidin-3-yl)morpholine

HRID 1922972
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인쇄 미리보기

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HRID 1922972 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[S: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)=[CH: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[S: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)=[CH:8][C:6]=2[N:7]=1
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참가 물질

7

반응물 3

HCID 10796Cesium carbonateHCID 596053422-Chloro-4-morpholin-4-yl-6-(3-morpholin-4-ylazetidin-1-ylmethyl)thieno[3,2-d]pyrimidineHCID 673417654,4,5,5-Tetramethyl-2-(2-methylbenzofuran-3-yl)-1,3,2-dioxaborolane

생성물 1

HCID 498324354-(1-((2-(2-Methylbenzofuran-3-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)azetidin-3-yl)morpholine수율 81%

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 2-chloro-4-morpholin-4-yl-6-(3-morpholin-4-ylazetidin-1-ylmethyl)thieno[3,2-d]pyrimidine (100 mg, 0.24 mmol), 2-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)benzofuran (94 mg, 0.36 mmol), tetrakis(triphenylphosphine)palladium (28 mg, 0.02 mmol) and Cs2CO3 (160 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, washed with DCM/MeOH then eluted with 2M NH3/MeOH. The resulting residue was purified by column chromatography (Si—PCC, MeOH:DCM, 0-5%) to afford 213 as a white foam (98 mg, 81%). LCMS (Method G): RT 9.09 min, [M+H]− 506.3. 1H NMR (CDCl3, 400 MHz): δ 8.42-8.39 (m, 1 H); 7.46-7.42 (m, 1 H); 7.32-7.24 (m, 3 H); 4.02 (t, J=4.7 Hz, 4H); 3.97 (s, 2 H); 3.89 (t, J=4.7 Hz, 4 H); 3.73 (m, 4 H); 3.63 (s, 2 H); 3.06 (m, 3 H); 2.93 (s, 3 H) and 2.33 (m, 4 H)

후처리

  1. customwas purged with argon
  2. washwashed with DCM/MeOH
  3. washthen eluted with 2M NH3/MeOH
  4. customThe resulting residue was purified by column chromatography (Si—PCC, MeOH:DCM, 0-5%)

출처 및 근거

ORD 기록
ord-43813dc9e45a4347b2b934213c07fd82
출처 데이터셋
uspto-grants-2012_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08173650B2

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