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

HRID 1945998ノート

反応式

HRID 1945998 の反応式
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]([CH:16]4[CH2:21][CH2:20][O:19][CH2:18][CH2:17]4)[CH2:13]3)[S:8][C:6]=2[N:7]=1.[CH2:28]([C:30]1[NH:31][C:32]2[CH:38]=[CH:37][CH:36]=[CH:35][C:33]=2[N:34]=1)[CH3:29].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]>[CH2:28]([C:30]1[N:31]([C:2]2[N:3]=[C:4]([N:22]3[CH2:23][CH2:24][O:25][CH2:26][CH2:27]3)[C:5]3[N:10]=[C:9]([CH2:11][N:12]4[CH2:13][CH:14]([CH:16]5[CH2:21][CH2:20][O:19][CH2:18][CH2:17]5)[CH2:15]4)[S:8][C:6]=3[N:7]=2)[C:32]2[CH:38]=[CH:37][CH:36]=[CH:35][C:33]=2[N:34]=1)[CH3:29]

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 158072-EthylbenzimidazoleHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 596060255-Chloro-7-morpholin-4-yl-2-[3-(tetrahydro-pyran-4-yl)azetidin-1-ylmethyl]thiazolo[5,4-d]pyrimidine

生成物 1

HCID 596052194-(5-(2-ethyl-1H-benzo[d]imidazol-1-yl)-2-((3-(tetrahydro-2H-pyran-4-yl)azetidin-1-yl)methyl)thiazolo[5,4-d]pyrimidin-7-yl)morpholine

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
145 °C

実験手順

A mixture of 5-chloro-7-morpholin-4-yl-2-[3-(tetrahydro-pyran-4-yl)azetidin-1-ylmethyl]thiazolo[5,4-d]pyrimidine (90 mg, 0.22 mmol), 2-ethylbenzimidazole (38 mg, 0.26 mmol), tris(dibenzylideneacetone)dipalladium (10 mg, 0.01 mmol), Xphos (21 mg, 0.04 mmol) and Cs2CO3 (143 mg, 0.44 mmol) in dioxane (2.5 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:EtOAc, 0-7%). The resulting residue was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH/DCM and the product eluted with 2M NH3/MeOH affording 483 as an orange solid (82 mg, 72%). LCMS (Method I): RT 2.70 min, [M+H]+ 520.2. 1H NMR (CDCl3, 400 MHz): δ 8.02-7.97 (m, 1 H); 7.76-7.71 (m, 1 H); 7.30-7.24 (m, 2 H); 4.41 (m, 4 H); 4.04-3.94 (m, 4 H); 3.91-3.82 (m, 4 H); 3.61 (m, 2 H); 3.44-3.30 (m, 4 H); 3.10 (m, 2 H); 2.40-2.30 (m, 1 H); 1.70 (m, 1 H); 1.55 (m, 2 H); 1.43 (t, J=7.5 Hz, 3 H) and 1.32-1.18 (m, 2 H)

後処理

  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, 0-7%)
  6. washwas washed with MeOH/DCM
  7. washthe product eluted with 2M NH3/MeOH affording 483 as an orange solid (82 mg, 72%)
  8. customRT 2.70 min, [M+H]+ 520.2

出典と根拠

ORDレコード
ord-b83e83e419e141fe8b74bed1749c54cd
出典データセット
uspto-grants-2013_03
特許番号
US08394796B2

反応ノート

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