三氟乙酸 → N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(3-cyano-4-(2-fluoropyridin-4-yl)phenyl)acetamide

HRID 1036282笔记

反应方程式

HRID 1036282 反应方程式
[C:1]([C:3]1[CH:4]=[C:5]([CH2:16][C:17]([O:19]C(C)(C)C)=O)[CH:6]=[CH:7][C:8]=1[C:9]1[CH:14]=[CH:13][N:12]=[C:11]([F:15])[CH:10]=1)#[N:2].[C:24](O)([C:26](F)(F)F)=[O:25].N1C=CN=CC=1[C:37]1[CH:38]=[CH:39][C:40]([NH2:43])=[N:41][CH:42]=1.CCN(C(C)C)C(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)[C:64]2[N:65]=[CH:66][CH:67]=C[C:63]=2[N:62]=N1>C(Cl)Cl>[C:24]([N:62]1[CH2:63][CH2:64][N:65]([C:37]2[CH:38]=[CH:39][C:40]([NH:43][C:17](=[O:19])[CH2:16][C:5]3[CH:6]=[CH:7][C:8]([C:9]4[CH:14]=[CH:13][N:12]=[C:11]([F:15])[CH:10]=4)=[C:3]([C:1]#[N:2])[CH:4]=3)=[N:41][CH:42]=2)[CH2:66][CH2:67]1)(=[O:25])[CH3:26]

参与物

7

反应物 5

HCID 6422三氟乙酸HCID 81531N,N-二异丙基乙胺HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59259225827588-90-9HCID 68247402Tert-butyl 2-(3-cyano-4-(2-fluoropyridin-4-yl)phenyl)acetate

产物 1

HCID 58447806N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(3-cyano-4-(2-fluoropyridin-4-yl)phenyl)acetamide

试剂、催化剂与溶剂 1

HCID 6344二氯甲烷溶剂

实验过程

A mixture of tert-butyl 2-(3-cyano-4-(2-fluoropyridin-4-yl)phenyl)acetate 206-5 (35 mg, 0.11 mmol) and TFA (0.5 mL) in DCM (3 mL) was stirred at room temperature for 5 hours. The solvents were evaporated to dryness under high vacuum. The crude product, 2-(3-cyano-4-(2-fluoropyridin-4-yl)phenyl)acetic acid 206-6, was dissolved in DMF (2 mL). 5-(pyrazin-2-yl)pyridin-2-amine (23 mg, 0.13 mmol) and DIEA (98 uL, 0.56 mmol) were added to the solution before O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluroniumhexafluorophosphate (64 mg, 0.17 mmol). The mixture was stirred at room temperature overnight. The mixture was stirred at room temperature overnight. The solvent was removed by rotary evaporation. The crude product was purified by reverse phase HPLC to give N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(3-cyano-4-(2-fluoropyridin-4-yl)phenyl)acetamide 206. MS m/z 411.2 (M+1); 1H NMR 400 MHz (MeOD) δ 9.09 (s, 1H), 9.01 (s, 1H), 8.66 (dd, 1H), 8.52 (d, 1H), 8.42 (dd, 1H), 8.32 (d, 1H), 8.25 (d, 1H), 7.92 (d, 1H), 7.81 (dd, 1H), 7.64 (d, 1H), 7.52 (dt, 1H), 7.28 (s, 1H), 3.93 (s, 2H).

后处理

  1. customThe solvents were evaporated to dryness under high vacuum
  2. dissolutionThe crude product, 2-(3-cyano-4-(2-fluoropyridin-4-yl)phenyl)acetic acid 206-6, was dissolved in DMF (2 mL)
  3. stirringThe mixture was stirred at room temperature overnight
  4. stirringThe mixture was stirred at room temperature overnight
  5. customThe solvent was removed by rotary evaporation
  6. customThe crude product was purified by reverse phase HPLC

来源与证据

ORD记录
ord-31dbcf255b05441e83e697cb02331c6c
来源数据集
uspto-grants-2013_10
专利号
US08546396B2

反应笔记

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