Triethylamine → 1-methyl-piperidine-4-carboxylic acid (1-{3-[5-carbamoyl-4-(3-chloro-phenyl)-thiazol-2-yl]-3H-benzoimidazol-5-ylmethyl}-piperidin-4-yl)-amide

HRID 1667706ノート

反応式

HRID 1667706 の反応式
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:10]=[CH:11][C:12]3[N:16]=[CH:15][N:14]([C:17]4[S:18][C:19]([C:29]([NH2:31])=[O:30])=[C:20]([C:22]5[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[CH:23]=5)[N:21]=4)[C:13]=3[CH:32]=2)[CH2:4][CH2:3]1.CN(C(N(C)C)=[N+]1C2C(=NC=CC=2)N=N1)C.F[P-](F)(F)(F)(F)F.[CH2:56]([N:58]([CH2:61][CH3:62])[CH2:59][CH3:60])C.[C:63]([O:67]C(NC(C)(C)C(O)=O)=O)(C)(C)[CH3:64]>C(OCC)(=O)C.CN(C)C=O>[C:29]([C:19]1[S:18][C:17]([N:14]2[C:13]3[CH:32]=[C:9]([CH2:8][N:5]4[CH2:4][CH2:3][CH:2]([NH:1][C:63]([CH:64]5[CH2:62][CH2:61][N:58]([CH3:56])[CH2:59][CH2:60]5)=[O:67])[CH2:7][CH2:6]4)[CH:10]=[CH:11][C:12]=3[N:16]=[CH:15]2)=[N:21][C:20]=1[C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[CH:23]=1)(=[O:30])[NH2:31]

参加物

8

反応物 5

HCID 8471TriethylamineHCID 9886HexafluorophosphateHCID 2733845N-((1,1-dimethylethoxy)carbonyl)-2-methyl-alanineHCID 468305822-[6-(4-Amino-piperidin-1-ylmethyl)-benzoimidazol-1-yl]-4-(3-chloro-phenyl)-thiazole-5-carboxylic acid amideHCID 178484285HCID 178484285、化合物

生成物 1

HCID 468305831-methyl-piperidine-4-carboxylic acid (1-{3-[5-carbamoyl-4-(3-chloro-phenyl)-thiazol-2-yl]-3H-benzoimidazol-5-ylmethyl}-piperidin-4-yl)-amide収率 54.8%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A mixture of 0.360 g (0.77 mmole) of 2-[6-(4-amino-piperidin-1-ylmethyl)-benzoimidazol-1-yl]-4-(3-chloro-phenyl)-thiazole-5-carboxylic acid amide (I.13), 5 mL of dimethylformamide, 0.441 g (1.16 mmole) of 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium, 3-oxide, hexafluorophosphate(1-) (1:1), 0.311 g (3.08 mmole) of triethylamine was stirred for 15 minutes, then 0.236 g (1.16 mmole) of 2-tert-butoxycarbonylamino-2-methyl-propionic acid was added. After 3 hours, the mixture was taken up in 100 mL of ethyl acetate, washed twice with 100 mL of water, and then once with 100 mL of brine. The ethyl acetate layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with dichloromethane-(methanol-ammonium hydroxide, (92.8:0.3)) (gradient 100:0-0:100) to give 0.250 g of 1-methyl-piperidine-4-carboxylic acid (1-{3-[5-carbamoyl-4-(3-chloro-phenyl)-thiazol-2-yl]-3H-benzoimidazol-5-ylmethyl}-piperidin-4-yl)-amide (I.15) as an off white solid. MH+/Z=652

後処理

  1. waitAfter 3 hours
  2. washwashed twice with 100 mL of water
  3. dry with materialThe ethyl acetate layer was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel chromatography
  7. washeluting with dichloromethane-(methanol-ammonium hydroxide, (92.8:0.3)) (gradient 100:0-0:100)

出典と根拠

ORDレコード
ord-58d83eb09879481293879e1ef03b1071
出典データセット
uspto-grants-2011_10
特許番号
US08044213B2

反応ノート

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