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 1667705

반응식

HRID 1667705 반응식
[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.C(N(CC)CC)C.[CH3:63][N:64]1[CH2:69][CH2:68][CH:67]([C:70](O)=[O:71])[CH2:66][CH2:65]1>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:70]([CH:67]5[CH2:68][CH2:69][N:64]([CH3:63])[CH2:65][CH2:66]5)=[O:71])[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]

참가 물질

8

반응물 5

HCID 8471TriethylamineHCID 9886HexafluorophosphateHCID 27369391-Methylpiperidine-4-carboxylic acidHCID 468305822-[6-(4-Amino-piperidin-1-ylmethyl)-benzoimidazol-1-yl]-4-(3-chloro-phenyl)-thiazole-5-carboxylic acid amideHCID 178484285HCID 178484285, 화합물

생성물 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

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

A mixture of 0.120 g (0.26 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, 0.148 g (0.39 mmole) of 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium, 3-oxide, hexafluorophosphate(1-) (1:1), 0.105 g (0.39 mmole) of triethylamine was stirred for 15 minutes, then 0.056 g (0.39 mmole) of 1-methyl-piperidine-4-carboxylic 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 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.14). This material was taken up in 20 mL of dichloromethane, washed with 20 mL of 1M sodium hydroxide solution. The dichloromethane layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give 0.065 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.14) as a solid. MH+/Z=592

후처리

  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)

출처 및 근거

ORD 기록
ord-5b5d6bbd4b7c485a8c62028f69d8242e
출처 데이터셋
uspto-grants-2011_10
특허 번호
US08044213B2

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