Cesium carbonate → 4-(1-((2-(2-isopropyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)methyl)azetidin-3-yl)morpholine

HRID 1946063

반응식

HRID 1946063 반응식
Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH2:12][N:13]3[CH2:16][CH:15]([N:17]4[CH2:22][CH2:21][O:20][CH2:19][CH2:18]4)[CH2:14]3)[N:8]2[CH3:11])=[C:4]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[N:3]=1.[CH:29]([C:32]1[NH:33][C:34]2[CH:40]=[CH:39][CH:38]=[CH:37][C:35]=2[N:36]=1)([CH3:31])[CH3:30].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]>[CH:29]([C:32]1[N:33]([C:2]2[N:10]=[C:9]3[C:5]([N:6]=[C:7]([CH2:12][N:13]4[CH2:14][CH:15]([N:17]5[CH2:22][CH2:21][O:20][CH2:19][CH2:18]5)[CH2:16]4)[N:8]3[CH3:11])=[C:4]([N:23]3[CH2:24][CH2:25][O:26][CH2:27][CH2:28]3)[N:3]=2)[C:34]2[CH:40]=[CH:39][CH:38]=[CH:37][C:35]=2[N:36]=1)([CH3:31])[CH3:30]

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 221212-(propan-2-yl)-1H-1,3-benzodiazoleHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 596058532-Chloro-9-methyl-6-morpholin-4-yl-8-(3-morpholin-4-ylazetidin-1-ylmethyl)-9H-purine

생성물 1

HCID 596060574-(1-((2-(2-isopropyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)methyl)azetidin-3-yl)morpholine수율 68%

시약·촉매·용매 2

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

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온도
145 °C

실험 절차

A mixture of 2-chloro-9-methyl-6-morpholin-4-yl-8-(3-morpholin-4-yl-azetidin-1-ylmethyl)-9H-purine (83 mg, 0.20 mmol), 2-isopropylbenzimidazole (39 mg, 0.24 mmol), tris(dibenzylideneacetone)dipalladium (9 mg, 0.01 mmol), Xphos (19 mg, 0.04 mmol) and Cs2CO3 (133 mg, 0.41 mmol) in dioxane (2 mL) was purged with argon then heated at 145° C. for 30 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:DCM, 0-15%) affording 547 as a beige foam (72 mg, 68%). LCMS (Method I): RT 2.50 min, [M+H]+ 532.3. 1H NMR (CDCl3, 400 MHz): δ 7.89-7.84 (m, 1 H); 7.80-7.75 (m, 1 H); 7.29-7.21 (m, 2 H); 4.34 (m, 4 H); 4.00-3.92 (m, 3 H); 3.88-3.81 (m, 7 H); 3.76 (m, 4 H); 3.64 (m, 2 H); 3.24 (m, 2 H); 3.13 (m, 1 H); 2.40 (m, 4 H); 1.47 (s, 3 H) and 1.46 (s, 3 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:DCM, 0-15%)

출처 및 근거

ORD 기록
ord-6d1cb7b121b54be5bfbf160ed510a20b
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08394796B2

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