1-Hydroxybenzotriazole → 1-Cyclobutyl-4-({1-[(2-methylpyrimidin-5-yl)carbonyl]azetidin-3-yl}carbonyl)-1,4-diazepane
反応式
[CH3:1][C:2]1[N:7]=[CH:6][C:5]([C:8]([OH:10])=O)=[CH:4][N:3]=1.C1C=CC2N(O)N=NC=2C=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH:45]1[CH2:48][CH:47]([C:49]([N:51]2[CH2:57][CH2:56][CH2:55][N:54]([CH:58]3[CH2:61][CH2:60][CH2:59]3)[CH2:53][CH2:52]2)=[O:50])[CH2:46]1>C(Cl)Cl>[CH:58]1([N:54]2[CH2:55][CH2:56][CH2:57][N:51]([C:49]([CH:47]3[CH2:46][N:45]([C:8]([C:5]4[CH:6]=[N:7][C:2]([CH3:1])=[N:3][CH:4]=4)=[O:10])[CH2:48]3)=[O:50])[CH2:52][CH2:53]2)[CH2:61][CH2:60][CH2:59]1参加物
6
反応物 4
生成物 1
試薬・触媒・溶媒 1
実験手順
To a stirred solution of 2-methylpyrimidine-5-carboxylic acid (23 mg, 0.17 mmol) in DCM (3 ml) was added HOBt (23 mg, 0.17 mmol) and HBTU (64 mg, 0.17 mmol). After 3 hours, a solution of 1-(Azetidin-3-ylcarbonyl)-4-cyclobutyl-1,4-diazepane (48 mg, 0.17 mmol), in DCM (1 ml) was added and the yellow suspension gradually dissolved to give a yellow solution. The reaction mixture was quenched with saturated NaHCO3 (1 ml) and the aqueous layer extracted with DCM (3×5 ml). The combined organic layers were dried (MgSO4), filtered and concentrated at reduced pressure. Purification by silica FCC (eluting with 99:1 to 95:5 gradient of DCM/2M NH3 in MeOH) gave the title compound (17.4 mg, 29% yield) as pale yellow oil.
後処理
- dissolutionthe yellow suspension gradually dissolved
- customto give a yellow solution
- customThe reaction mixture was quenched with saturated NaHCO3 (1 ml)
- extractionthe aqueous layer extracted with DCM (3×5 ml)
- dry with materialThe combined organic layers were dried (MgSO4)
- filtrationfiltered
- concentrationconcentrated at reduced pressure
- customPurification
- washby silica FCC (eluting with 99:1 to 95:5 gradient of DCM/2M NH3 in MeOH)
出典と根拠
- ORDレコード
- ord-e212567aa90c44e99f0b2b2f7a51a8b9
- 出典データセット
- uspto-grants-2014_12
- 特許番号
- US08912176B2
反応ノート
読み込み中…