Triethylamine → N-(4-(4-Ethylaminopyrimidin-6-yl-oxy)-phenyl)-N'[(R)-5-bromo-indan-2-yl]-urea

HRID 1993525ノート

反応式

HRID 1993525 の反応式
Cl[C:2](Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.[Br:13][C:14]1[CH:15]=[C:16]2[C:20](=[CH:21][CH:22]=1)[CH2:19][C@@H:18]([NH2:23])[CH2:17]2.CCN(CC)CC.[CH2:31]([NH:33][C:34]1[CH:39]=[C:38]([O:40][C:41]2[CH:47]=[CH:46][C:44]([NH2:45])=[CH:43][CH:42]=2)[N:37]=[CH:36][N:35]=1)[CH3:32]>C(Cl)Cl>[CH2:31]([NH:33][C:34]1[CH:39]=[C:38]([O:40][C:41]2[CH:47]=[CH:46][C:44]([NH:45][C:2]([NH:23][C@H:18]3[CH2:17][C:16]4[C:20](=[CH:21][CH:22]=[C:14]([Br:13])[CH:15]=4)[CH2:19]3)=[O:4])=[CH:43][CH:42]=2)[N:37]=[CH:36][N:35]=1)[CH3:32]

参加物

6

反応物 4

HCID 8471Triethylamine2 回HCID 94429TriphosgeneHCID 112758701H-Inden-2-amine, 5-bromo-2,3-dihydro-, (2R)-HCID 586593854-(4-Ethylaminopyrimidin-6-yloxy)aniline

生成物 1

HCID 58659333N-(4-(4-Ethylaminopyrimidin-6-yl-oxy)-phenyl)-N'[(R)-5-bromo-indan-2-yl]-urea

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒3 回

実験手順

A solution of triphosgene (117 mg, 0.393 mmol) in CH2Cl2 (12 ml) under N2-atmosphere is cooled by an ice bath. A solution of [(R)-5-bromo-indan-2-yl-amine (250 mg, 1.178 mmol; preparation see Adv. Synth. Catal. 2001, 343, 461) and NEt3 (164 μl; 1.177 mmol) in CH2Cl2 (10 ml) is added dropwise, the dropping funnel rinsed with CH2Cl2 (2 ml) and the resulting suspension stirred for 60 min at rt. Then a solution of 4-(4-ethylaminopyrimidin-6-yl-oxy)-aniline (258 mg, 1.12 mmol) and NEt3 (164 μl; 1.177 mmol) in CH2Cl2 (10 ml) is added dropwise and the dropping funnel rinsed with CH2Cl2 (2 ml). A brown solution is formed, which is stirred for 16 h at rt. SiO2 is then added to the resulting mixture. After concentration in vacuo, the powder is put on top of a MPLC column (SiO2). Eluation with SiO2/AcOEt 4:1→AcOEt, partial concentration and filtration of the crystallized material yields the title compound: m.p.: 247° C.; 1H-NMR (DMSO-d6): 8.33 (s, 1H), 8.06 (s, 1H), 7.43 (s, 1H), 7.36 (d, 2H), 7.30 (m, 1H), 7.26 (t, 1H), 7.19 (d, 1H), 6.96 (d, 2H), 6.43 (d, 1H), 5.63 (s, 1H), 4.40 (m, 1H), 3.2 (m, 4H), 2.75 (AB×d, 2H), 1.07 (t, 3H); Anal.: CHNBr.

後処理

  1. washthe dropping funnel rinsed with CH2Cl2 (2 ml)
  2. washthe dropping funnel rinsed with CH2Cl2 (2 ml)
  3. customA brown solution is formed
  4. stirringwhich is stirred for 16 h at rt
  5. additionSiO2 is then added to the resulting mixture
  6. concentrationAfter concentration in vacuo
  7. concentrationEluation with SiO2/AcOEt 4:1→AcOEt, partial concentration and filtration of the crystallized material

出典と根拠

ORDレコード
ord-830bbe3f7f5e40ac9588f79378cfb888
出典データセット
uspto-grants-2010_01
特許番号
US07652022B2

反応ノート

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