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

HRID 1993525Notes

Reaction equation

HRID 1993525 reaction equation
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]

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-830bbe3f7f5e40ac9588f79378cfb888
Source dataset
uspto-grants-2010_01
Patent number
US07652022B2

Reaction notes

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