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Cesium carbonate → 4-(5-(2-methyl-1H-benzo[d]imidazol-1-yl)-2-((3-(1,1-dioxo-thiomorpholino)azetidin-1-yl)methyl)thiazolo[5,4-d]pyrimidin-7-yl)morpholine

HRID 1923148
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HRID 1923148 반응식
Cl[C:2]1[N:3]=[C:4]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[C:5]2[N:10]=[C:9]([CH2:11][N:12]3[CH2:15][CH:14]([N:16]4[CH2:21][CH2:20][S:19](=[O:23])(=[O:22])[CH2:18][CH2:17]4)[CH2:13]3)[S:8][C:6]=2[N:7]=1.[CH3:30][C:31]1[NH:32][C:33]2[CH:39]=[CH:38][CH:37]=[CH:36][C:34]=2[N:35]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:30][C:31]1[N:35]([C:2]2[N:3]=[C:4]([N:24]3[CH2:25][CH2:26][O:27][CH2:28][CH2:29]3)[C:5]3[N:10]=[C:9]([CH2:11][N:12]4[CH2:13][CH:14]([N:16]5[CH2:17][CH2:18][S:19](=[O:22])(=[O:23])[CH2:20][CH2:21]5)[CH2:15]4)[S:8][C:6]=3[N:7]=2)[C:34]2[CH:36]=[CH:37][CH:38]=[CH:39][C:33]=2[N:32]=1
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참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 119842-MethylbenzimidazoleHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 596058185-Chloro-2-[3-(1,1-Dioxo-1-thiomorpholin-4-yl)azetidin-1-ylmethyl]-7-morpholin-4-ylthiazolo[5,4-d]pyrimidine

생성물 1

HCID 596056864-(5-(2-methyl-1H-benzo[d]imidazol-1-yl)-2-((3-(1,1-dioxo-thiomorpholino)azetidin-1-yl)methyl)thiazolo[5,4-d]pyrimidin-7-yl)morpholine
수율 40.4%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매

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온도
145 °C

실험 절차

A mixture of 5-chloro-2-[3-(1,1-dioxo-1-thiomorpholin-4-yl)azetidin-1-ylmethyl]-7-morpholin-4-ylthiazolo[5,4-d]pyrimidine (150 mg, 0.33 mmol), 2-methylbenzimidazole (52 mg, 0.39 mmol), tris(dibenzylideneacetone)dipalladium (15 mg, 0.02 mmol), Xphos (31 mg, 0.07 mmol) and Cs2CO3 (213 mg, 0.65 mmol) in dioxane (3 mL) was purged with argon then heated at 145° C. for 45 min in a microwave reactor. The reaction mixture was filtered through a pad of celite, washing with EtOAc. The filtrate was concentrated in vacuo and purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-5%) affording 448 as a foam (74 mg, 40%). LCMS (Method I): RT 2.45 min, [M+H]+ 555.2. 1H NMR (CDCl3, 400 MHz): δ 8.09-8.04 (m, 1 H); 7.74-7.69 (m, 1 H); 7.34-7.26 (m, 2 H); 4.41 (m, 4 H); 4.01 (s, 2 H); 3.88 (m, 4 H); 3.71 (t, J=6.7 Hz, 2 H); 3.37-3.30 (m, 1 H); 3.15 (t, J=6.7 Hz, 2 H); 3.09 (m, 4 H); 2.94 (s, 3 H) and 2.88 (m, 4 H)

후처리

  1. customwas purged with argon
  2. filtrationThe reaction mixture was filtered through a pad of celite
  3. washwashing with EtOAc
  4. concentrationThe filtrate was concentrated in vacuo
  5. custompurified by column chromatography (Si—PCC, MeOH:EtOAc, 0-5%)

출처 및 근거

ORD 기록
ord-774f35bb3c3d4e97a19b96635e0508c6
출처 데이터셋
uspto-grants-2012_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08173650B2

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