1,2-Dimethoxyethane → HCID 67682236、化合物

HRID 1751582ノート

反応式

HRID 1751582 の反応式
CC1(C)C(C)(C)OB([C:9]2[CH:22]=[C:21]3[C:12]([C:13]4[CH:14]=[CH:15][C:16]([C:23]5[CH:24]=[CH:25][C:26]6[N:30]=[C:29]([C@@H:31]7[CH2:35][CH2:34][CH2:33][N:32]7[C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[NH:28][C:27]=6[CH:43]=5)=[CH:17][C:18]=4[CH2:19][CH2:20]3)=[CH:11][CH:10]=2)O1.Br[C:46]1[NH:50][C:49]([C@@H:51]2[CH2:55][CH2:54][CH2:53][N:52]2[C:56](=[O:66])[C@@H:57]([NH:61][C:62](=[O:65])[O:63][CH3:64])[CH:58]([CH3:60])[CH3:59])=[N:48][CH:47]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(COC)OC>C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:64][O:63][C:62]([NH:61][C@@H:57]([CH:58]([CH3:60])[CH3:59])[C:56]([N:52]1[CH2:53][CH2:54][CH2:55][C@H:51]1[C:49]1[NH:50][C:46]([C:9]2[CH:22]=[C:21]3[C:12]([C:13]4[CH:14]=[CH:15][C:16]([C:23]5[CH:24]=[CH:25][C:26]6[N:30]=[C:29]([C@@H:31]7[CH2:35][CH2:34][CH2:33][N:32]7[C:36]([O:38][C:39]([CH3:41])([CH3:40])[CH3:42])=[O:37])[NH:28][C:27]=6[CH:43]=5)=[CH:17][C:18]=4[CH2:19][CH2:20]3)=[CH:11][CH:10]=2)=[CH:47][N:48]=1)=[O:66])=[O:65]

参加物

8

反応物 4

HCID 80711,2-DimethoxyethaneHCID 62657Potassium Phosphate, TribasicHCID 56605304methyl ((S)-1-((S)-2-(5-bromo-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl)carbamateHCID 67682289(S)-tert-butyl 2-(6-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9,10-dihydrophenanthren-2-yl)-1H-benzo[d]imidazol-2-yl)pyrrolidine-1-carboxylate

生成物 1

HCID 67682236HCID 67682236、化合物収率 4%

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒2 回HCID 178418397HCID 178418397、化合物触媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
90 °C

実験手順

A mixture of (S)-tert-butyl 2-(6-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9,10-dihydrophenanthren-2-yl)-1H-benzo[d]imidazol-2-yl)pyrrolidine-1-carboxylate (590 mg, 1.0 mmol), methyl (S)-1-((S)-2-(5-bromo-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (492 mg, 1.3 mmol), PdCl2(dppf) (37 mg, 0.05 mmol), 2M aqueous potassium phosphate solution (1.5 mL, 3.0 mmol), and dimethoxyethane (5 mL) was degassed with a stream of argon for twenty minutes. The reaction was heated to 90° C. After one hour, the reaction was cooled to room temperature and tetrakis(triphenylphosphine)palladium(0) (58 mg, 0.05 mmol) was added. The reaction was heated to 90° C. After three hours, the reaction was cooled to room temperature and more PdCl2(dppf) (37 mg, 0.05 mmol) was added. The reaction was heated to 80° C. After 16 hours, the reaction was cooled to room temperature and diluted with ethyl acetate. The organic phase was washed with water and brine, dried (Na2SO4) and concentrated. The resulting residue was purified by flash column chromatography to yield (S)-tert-butyl 2-(6-(7-(2-((S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)-9,10-dihydrophenanthren-2-yl)-1H-benzo[d]imidazol-2-yl)pyrrolidine-1-carboxylate (30 mg, 4%).

後処理

  1. customwas degassed with a stream of argon for twenty minutes
  2. temperaturethe reaction was cooled to room temperature
  3. temperatureThe reaction was heated to 90° C
  4. waitAfter three hours
  5. temperaturethe reaction was cooled to room temperature
  6. temperatureThe reaction was heated to 80° C
  7. waitAfter 16 hours
  8. temperaturethe reaction was cooled to room temperature
  9. washThe organic phase was washed with water and brine
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated
  12. customThe resulting residue was purified by flash column chromatography

出典と根拠

ORDレコード
ord-38f28ced86334bc28945a2ee79b66357
出典データセット
uspto-grants-2015_10
特許番号
US09156823B2

反応ノート

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