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llms.txt · MCP 가이드개인정보처리방침 · 이용약관 · 지원v1.8.0
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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
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HRID 1972800 반응식
[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]
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참가 물질

9

반응물 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

생성물 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 ester수율 165.8%

시약·촉매·용매 4

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 10340Sodium Carbonate용매HCID 24437Sodium Sulfite용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-b751f18fc1ae4fa48bbf17ac1111d24d
출처 데이터셋
uspto-grants-2013_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08431695B2

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