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1,3-Dibromo-5,5-dimethylhydantoin → 4-[3-(4-Amino-5-bromo-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-Phenyl]-piperazine-1-carboxylic acid tert-butyl ester

HRID 1972800
ノート
印刷プレビュー

反応式

HRID 1972800 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([C:20]3[N:28]4[C:23]([C:24]([NH2:29])=[N:25][CH:26]=[N:27]4)=[CH:22][CH:21]=3)[CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1COCC1.[Br:35]N1C(C)(C)C(=O)N(Br)C1=O.CCOC(C)=O>CN(C=O)C.C([O-])([O-])=O.[Na+].[Na+].[O-]S([O-])=O.[Na+].[Na+].O>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][N:11]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([C:20]3[N:28]4[C:23]([C:24]([NH2:29])=[N:25][CH:26]=[N:27]4)=[C:22]([Br:35])[CH:21]=3)[CH:15]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
参加物実験手順後処理出典と根拠反応ノート

参加物

9

反応物 4

HCID 64791,3-Dibromo-5,5-dimethylhydantoinHCID 8028TetrahydrofuranHCID 8857Ethyl AcetateHCID 585296384-[3-(4-Amino-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-phenyl]-piperazine-1-carboxylic acid tert-butyl ester

生成物 1

HCID 585297564-[3-(4-Amino-5-bromo-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-Phenyl]-piperazine-1-carboxylic acid tert-butyl ester収率 165.8%

試薬・触媒・溶媒 4

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 10340Sodium Carbonate溶媒HCID 24437Sodium Sulfite溶媒

実験手順

The product from step 3 (160 mg. 0.40 mmol) was dissolved in 1 mL of DMF and 1 mL of THF was added. The mixture was cooled to −20° C. (isopropanol/ice/dry ice bath) and 1,3-dibromo-5,5-dimethyl hydantoin (58 mg, 0.20 mmol) was added in 4 portions over 40 minutes. The mixture was stirred for an additional 1 hour during which the internal temp rose to −5° C. It was diluted with a mixture of 1 mL of 2M Na2CO3, 1 mL of sat. Na2SO3 and 6 mL of water and the mixture stirred for 5 minutes. EtOAc (10 mL) was added and the layers were separated. The aqueous layer was extracted with 15 mL of EtOAc and the combined organic fractions were washed with 2M aqueous Na2CO3, water, brine, dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by Isco®(Red-sep 12, eluting with 60-100% hexanes/EtOAc) to provide 157 mg (82%) of the title compound as a foamy solid. 1H-NMR (DMSO-d6) 7.98-7.64 (bs, 2H), 7.61 (s, 1H), 7.797 (s, 1H), 7.52 (d, 1H), 7.03 (d, 1H), 7.00-6.93 (m, 2H), (d, 1H), 6.71 (d, 1H), 3.43 (m, 4H), 3.13 (m, 4H), 1.40 (s, 9H); LC-MS [M+H]+=473, 475, RT=2.80 min.

後処理

  1. additionwas added in 4 portions over 40 minutes
  2. customrose to −5° C
  3. stirringthe mixture stirred for 5 minutes
  4. customthe layers were separated
  5. extractionThe aqueous layer was extracted with 15 mL of EtOAc
  6. washthe combined organic fractions were washed with 2M aqueous Na2CO3, water, brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by Isco®(Red-sep 12
  11. washeluting with 60-100% hexanes/EtOAc)

出典と根拠

ORDレコード
ord-b751f18fc1ae4fa48bbf17ac1111d24d
出典データセット
uspto-grants-2013_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08431695B2

反応ノート

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