Hydrochloric Acid → HCID 178502338、化合物

HRID 1751672ノート

反応式

HRID 1751672 の反応式
[Br:1][C:2]1[C:3]([F:27])=[C:4]2[C:24](=[CH:25][CH:26]=1)[C:8]1[NH:9][C:10]([C@@H:12]3[CH2:16][CH2:15][CH2:14][N:13]3[C:17](OC(C)(C)C)=[O:18])=[N:11][C:7]=1[CH:6]=[CH:5]2.Cl.[CH3:29][O:30][C:31]([NH:33][C@@H:34]([CH:38]([CH3:40])[CH3:39])C(O)=O)=[O:32].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>C(Cl)Cl.CCOC(C)=O.CN(C=O)C.CO>[Br:1][C:2]1[C:3]([F:27])=[C:4]2[C:24](=[CH:25][CH:26]=1)[C:8]1[NH:9][C:10]([C@@H:12]3[CH2:16][CH2:15][CH2:14][N:13]3[C:17](=[O:18])[C@@H:34]([NH:33][C:31](=[O:32])[O:30][CH3:29])[CH:38]([CH3:40])[CH3:39])=[N:11][C:7]=1[CH:6]=[CH:5]2

参加物

10

反応物 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10942966(2S)-2-((methoxycarbonyl)amino)-3-methylbutanoic acidHCID 178451894(S)-tert-butyl 2-(7-bromo-6-fluoro-1H-naphtho[1,2-d]imidazol-2-yl)pyrrolidine-1-carboxylate

生成物 1

HCID 178502338HCID 178502338、化合物収率 103.1%

試薬・触媒・溶媒 4

HCID 887Methanol溶媒HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

(S)-tert-butyl 2-(7-bromo-6-fluoro-1H-naphtho[1,2-d]imidazol-2-yl)pyrrolidine-1-carboxylate (204 mg, 0.47 mmol) was dissolved in DCM (5 mL), MeOH (1 mL) and HCl (4 M in dioxane, 1 mL) was added. The reaction mixture was stirred for 16 h and then concentrated under reduced pressure. The crude residue was treated with (S)-2-(methoxycarbonylamino)-3-methylbutanoic acid (82 mg, 0.47 mmol), HATU (179 mg, 0.47 mmol) and DMF (6 mL), then DIPEA (0.41 mL, 2.35 mmol) was added dropwise. After 3 h, the mixture was diluted with EtOAc and washed successively with saturated aqueous NaHCO3 and brine. The organics were dried over MgSO4, filtered and concentrated under reduced pressure. The crude residue was purified by silica column chromatography (0% to 30% MeOH/EtOAc) to afford methyl (S)-1-((S)-2-(7-bromo-6-fluoro-1H-naphtho[1,2-d]imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (238 mg, 49%).

後処理

  1. concentrationconcentrated under reduced pressure
  2. waitAfter 3 h
  3. washwashed successively with saturated aqueous NaHCO3 and brine
  4. dry with materialThe organics were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude residue was purified by silica column chromatography (0% to 30% MeOH/EtOAc)

出典と根拠

ORDレコード
ord-ad716fb9a3bd4df49b5062344a9a45b3
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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