4,5-双二苯基膦-9,9-二甲基氧杂蒽 → (R)-2-(4-cyano-3-(3-methylisothiazol-5-ylamino)phenylamino)-3-(thiophen-2-yl)propanamide

HRID 2201126

反应方程式

HRID 2201126 反应方程式
Br[C:2]1[CH:3]=[C:4]([NH:10][C@H:11]([CH2:15][C:16]2[S:17][CH:18]=[CH:19][CH:20]=2)[C:12]([NH2:14])=[O:13])[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].Cl.[NH2:22][C:23]1[S:27][N:26]=[C:25]([CH3:28])[CH:24]=1.O.O.O.[O-]C1C=CC=CC=1.[Na+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>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]>[C:8]([C:7]1[CH:6]=[CH:5][C:4]([NH:10][C@H:11]([CH2:15][C:16]2[S:17][CH:18]=[CH:19][CH:20]=2)[C:12]([NH2:14])=[O:13])=[CH:3][C:2]=1[NH:22][C:23]1[S:27][N:26]=[C:25]([CH3:28])[CH:24]=1)#[N:9]

参与物

7

反应物 4

HCID 6360444,5-双二苯基膦-9,9-二甲基氧杂蒽HCID 27239185-氨基-3-甲基异噻唑HCID 23681143苯酚钠HCID 67508155(R)-2-(3-bromo-4-cyanophenylamino)-3-(thiophen-2-yl)propanamide

产物 1

HCID 67508797(R)-2-(4-cyano-3-(3-methylisothiazol-5-ylamino)phenylamino)-3-(thiophen-2-yl)propanamide收率 33.9%

试剂、催化剂与溶剂 2

HCID 9811564三(二亚苄基丙酮)二钯催化剂HCID 312751,4-二氧六环溶剂

实验过程

A mixture of (R)-2-(3-bromo-4-cyanophenylamino)-3-(thiophen-2-yl)propanamide (35 mg, 0.100 mmol), 5-amino-3-methylisothiazole hydrochloride (25 mg, 0.166 mmol), sodium phenoxide trihydrate (52 mg, 0.305 mmol), xantphos (14 mg, 0.024 mmol) and Pd2 dba3 (10 mg, 0.010 mmol) in dioxane (2 mL) was degassed with argon, then was heated by microwave at 170 C for 30 min. The mixture was concentrated in vacuo. The residue was purified by HPLC to give (R)-2-(4-cyano-3-(3-methylisothiazol-5-ylamino)phenylamino)-3-(thiophen-2-yl)propanamide (13 mg).

后处理

  1. customwas degassed with argon
  2. temperaturewas heated by microwave at 170 C for 30 min
  3. concentrationThe mixture was concentrated in vacuo
  4. customThe residue was purified by HPLC

来源与证据

ORD记录
ord-06fbf081666d425e8da0bae9566d859b
来源数据集
uspto-grants-2016_06
专利号
US09359375B2

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