Hydrochloric Acid → 2-(4'-Bromo-biphenyl-4-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1185771

反応式

HRID 1185771 の反応式
C(O[C:6](=[O:21])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][C:17]([Br:20])=[CH:16][CH:15]=2)=[CH:10][CH:9]=1)(C)(C)C.Cl.[N:23]1([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:30][CH2:29][CH2:28][C@H:24]1C(O)=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CO.CN(C=O)C.C(OCC)(=O)C>[C:34]([O:33][C:31]([N:23]1[CH2:30][CH2:29][CH2:28][CH:24]1[C:6](=[O:21])[NH:7][C:8]1[CH:9]=[CH:10][C:11]([C:14]2[CH:15]=[CH:16][C:17]([Br:20])=[CH:18][CH:19]=2)=[CH:12][CH:13]=1)=[O:32])([CH3:37])([CH3:35])[CH3:36]

参加物

9

反応物 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 596105344-Bromo-4'-t-butoxycarbonylaminobiphenyl

生成物 1

HCID 666213242-(4'-Bromo-biphenyl-4-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester収率 95.2%

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
60 °C

実験手順

(4′-Bromo-biphenyl-4-yl)-carbamic acid tert-butyl ester (407 mg, 1.17 mmol) was dissolved in methanol (10 mL) and concentrated HCl (2 mL) was added. The solution was stirred at 60° C. for 1 hour then concentrated. The crude residue was treated with Boc-Pro-OH (302 mg, 1.40 mmol) and HATU (578 mg, 1.52 mmol) and suspended in DMF (6 mL). DIPEA (1.02 mL, 5.85 mmol) was added and the reaction mixture was stirred at RT for 4 hours after which it was diluted with ethyl acetate (200 mL) and washed with water and brine. The organic phase was dried over magnesium sulfate and concentrated. The residue was purified by silica column chromatography (30% to 55% EtOAc/hexanes) to afford 2-(4′-Bromo-biphenyl-4-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (496 mg, 95% over 2 steps).

後処理

  1. concentrationthen concentrated
  2. stirringthe reaction mixture was stirred at RT for 4 hours after which it
  3. washwashed with water and brine
  4. dry with materialThe organic phase was dried over magnesium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by silica column chromatography (30% to 55% EtOAc/hexanes)

出典と根拠

ORDレコード
ord-a2d7e37ab62f41daa0c2ef44c364da68
出典データセット
uspto-grants-2014_03
特許番号
US08669234B2

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