Hydrochloric Acid → (S)-2-amino-N-((2-(7-(4-(3-(2,4-difluorophenyl)ureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-1-methyl-1H-imidazol-5-yl)methyl)-N-(2-methoxyethyl)-3-methylbutanamide

HRID 409982ノート

反応式

HRID 409982 の反応式
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10](=[O:55])[NH:11][C:12]1[CH:53]=[CH:52][C:15]([O:16][C:17]2[CH:22]=[CH:21][N:20]=[C:19]3[CH:23]=[C:24]([C:26]4[N:27]([CH3:51])[C:28]([CH2:31][N:32]([CH2:47][CH2:48][O:49][CH3:50])[C:33](=[O:46])[C@@H:34]([NH:38]C(=O)OC(C)(C)C)[CH:35]([CH3:37])[CH3:36])=[CH:29][N:30]=4)[S:25][C:18]=23)=[C:14]([F:54])[CH:13]=1.Cl.O1CCOCC1>C(Cl)Cl.O.C([O-])(O)=O.[Na+]>[NH2:38][C@@H:34]([CH:35]([CH3:37])[CH3:36])[C:33]([N:32]([CH2:31][C:28]1[N:27]([CH3:51])[C:26]([C:24]2[S:25][C:18]3[C:19](=[N:20][CH:21]=[CH:22][C:17]=3[O:16][C:15]3[CH:52]=[CH:53][C:12]([NH:11][C:10]([NH:9][C:3]4[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=4[F:1])=[O:55])=[CH:13][C:14]=3[F:54])[CH:23]=2)=[N:30][CH:29]=1)[CH2:47][CH2:48][O:49][CH3:50])=[O:46]

参加物

7

反応物 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 67048306(S)-tert-butyl 1-(((2-(7-(4-(3-(2,4-difluorophenyl)ureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-1-methyl-1H-imidazol-5-yl)methyl)(2-methoxyethyl)amino)-3-methyl-1-oxobutan-2-ylcarbamate

生成物 1

HCID 67048202(S)-2-amino-N-((2-(7-(4-(3-(2,4-difluorophenyl)ureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-1-methyl-1H-imidazol-5-yl)methyl)-N-(2-methoxyethyl)-3-methylbutanamide収率 89%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6344Dichloromethane溶媒HCID 516892Sodium Bicarbonate溶媒

実験手順

To a suspension of the compound 352 (200 mg, 0.256 mmol) in DCM (10 ml) was added HCl in dioxane (0.7 ml, 10.95 eq, 2.80 mmol, 4M in dioxane) and the reaction mixture was stirred at RT for 3 hours. The mixture wad diluted with water and solid NaHCO3 was added. The reaction mixture was extracted with EtOAc then the organic phase was collected, dried over Na2SO4, filtered and concentrated. Purification of the residue by column chromatography (eluent 30% MeOH in EtOAc) afforded the desired compound 353 as pale yellow powder (155 mg, 89% yield). 1H NMR (d6-DMSO) 9.36 (s, 1H), 8.60 (s, 1H), 8.49 (m, 1H), 8.01 (m, 1H), 7.87 (s, 1H), 7.71 (m, 1H), 7.41 (t, J=8.99 Hz, 1H), 7.31 (m, 1H), 7.20 (m, 1H), 7.02 (m, 1H), 6.98 (s, 1H), 6.65 (d, J=5.09 Hz, 1H), 4.83 (d, J=15.65 Hz, 1H), 4.48 (d, J=15.65 Hz, 1H), 3.81 (s, 1H), 3.80 (s, 2H), 3.40 (m, 1H), 3.39-3.295 (m, 6H), 1.71 (m, 2H), 0.81 (m, 6H).

後処理

  1. additionwas added
  2. extractionThe reaction mixture was extracted with EtOAc
  3. customthe organic phase was collected
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification of the residue by column chromatography (eluent 30% MeOH in EtOAc)

出典と根拠

ORDレコード
ord-6b0d0ae794454df0a480e712135ab26c
出典データセット
uspto-grants-2014_06
特許番号
US08759522B2

反応ノート

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