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三氟乙酸 → 4-[3-((R)-3-Amino-6,6-difluoro-5-methyl-2,5,6,7-tetrahydro-[1,4]oxazepin-5-yl)-4-fluoro-phenylamino]-benzonitrile

HRID 403274
笔记
打印预览

反应方程式

HRID 403274 反应方程式
COC1C=CC(C(C2C=CC(OC)=CC=2)([NH:16][C:17]2[CH2:18][O:19][CH2:20][C:21]([F:42])([F:41])[C@:22]([C:25]3[CH:26]=[C:27]([NH:32][C:33]4[CH:40]=[CH:39][C:36]([C:37]#[N:38])=[CH:35][CH:34]=4)[CH:28]=[CH:29][C:30]=3[F:31])([CH3:24])[N:23]=2)C2C=CC=CC=2)=CC=1.FC(F)(F)C(O)=O.C([O-])([O-])=O.[Na+].[Na+]>ClCCl>[NH2:16][C:17]1[CH2:18][O:19][CH2:20][C:21]([F:41])([F:42])[C@:22]([C:25]2[CH:26]=[C:27]([NH:32][C:33]3[CH:40]=[CH:39][C:36]([C:37]#[N:38])=[CH:35][CH:34]=3)[CH:28]=[CH:29][C:30]=2[F:31])([CH3:24])[N:23]=1
参与物反应条件实验过程后处理来源与证据反应笔记

参与物

5

反应物 3

HCID 6422三氟乙酸HCID 10340Carbonic acid sodium salt (1:2)HCID 68227192(R)-4-(3-(3-(bis(4-methoxyphenyl)(phenyl)methylamino)-6,6-difluoro-5-methyl-2,5,6,7-tetrahydro-1,4-oxazepin-5-yl)-4-fluorophenylamino)benzonitrile

产物 1

HCID 665473204-[3-((R)-3-Amino-6,6-difluoro-5-methyl-2,5,6,7-tetrahydro-[1,4]oxazepin-5-yl)-4-fluoro-phenylamino]-benzonitrile收率 76.7%

试剂、催化剂与溶剂 1

HCID 6344
二氯甲烷
溶剂

反应条件

温度
23 °C

实验过程

To a solution of (R)-4-(3-(3-(bis(4-methoxyphenyl)(phenyl)methylamino)-6,6-difluoro-5-methyl-2,5,6,7-tetrahydro-1,4-oxazepin-5-yl)-4-fluorophenylamino)benzonitrile (intermediate A13A) (21 mg, 31 μmol) in dichloromethane (1 ml) at 23° C. was added trifluoroacetic acid (370 mg, 250 μl, 3.24 mmol) and the mixture was stirred at 23° C. for 1 h. Poured into sat. Na2CO3-sol., extracted thrice with ethyl acetate, dried the combined organic layer over Na2SO4. Removal of the solvent in vacuum left a crude product, which was purified by preparative HPLC (column: Gemini 5μ C18 110 A° AXIA (50×21.2 mm); flow: 40 ml/min; gradient: water (+0.1% TEA)/acetonitrile (90%-10% 1 min plateau; in 3.5 min to 5%-95%); collection: UV-detector 300 nm) to give the title compound (8.9 mg, 76.6%) after trituration with little diethyl ether/pentane as a white solid. MS (ISP): m/z=375.3 [M+H]+.

后处理

  1. extraction, extracted thrice with ethyl acetate
  2. dry with materialdried the combined organic layer over Na2SO4
  3. customRemoval of the solvent in vacuum
  4. waitleft a crude product, which
  5. customwas purified by preparative HPLC (column: Gemini 5μ C18 110 A° AXIA (50×21.2 mm); flow: 40 ml/min; gradient: water (+0.1% TEA)/acetonitrile (90%-10% 1 min plateau; in 3.5 min to 5%-95%); collection: UV-detector 300 nm)

来源与证据

ORD记录
ord-d0ca0c26c12c4c0cbfd61d4731c4f001
来源数据集
uspto-grants-2014_06
DOI
10.6084/m9.figshare.5104873.v1
专利号
US08748418B2

反应笔记

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本页导航参与物反应条件实验过程后处理来源与证据反应笔记