Acetic Acid → 5-(5-{[4-(hydroxymethyl)piperidin-1-yl]methyl}-1-benzofuran-2-yl)-4-[(4-methyl-1H-indol-5-yl)amino]nicotinonitrile

HRID 506195노트

반응식

HRID 506195 반응식
[CH:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:10][C:9]([C:11]3[CH:12]=[N:13][CH:14]=[C:15]([C:18]=3[NH:19][C:20]3[C:21]([CH3:29])=[C:22]4[C:26](=[CH:27][CH:28]=3)[NH:25][CH:24]=[CH:23]4)[C:16]#[N:17])=[CH:8][C:7]=2[CH:30]=1)=[O:2].[OH:31][CH2:32][CH:33]1[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.CN1C(=O)CCC1>[OH:31][CH2:32][CH:33]1[CH2:38][CH2:37][N:36]([CH2:1][C:3]2[CH:4]=[CH:5][C:6]3[O:10][C:9]([C:11]4[CH:12]=[N:13][CH:14]=[C:15]([C:18]=4[NH:19][C:20]4[C:21]([CH3:29])=[C:22]5[C:26](=[CH:27][CH:28]=4)[NH:25][CH:24]=[CH:23]5)[C:16]#[N:17])=[CH:8][C:7]=3[CH:30]=2)[CH2:35][CH2:34]1.[OH:2][CH2:1][C:3]1[CH:4]=[CH:5][C:6]2[O:10][C:9]([C:11]3[CH:12]=[N:13][CH:14]=[C:15]([C:18]=3[NH:19][C:20]3[C:21]([CH3:29])=[C:22]4[C:26](=[CH:27][CH:28]=3)[NH:25][CH:24]=[CH:23]4)[C:16]#[N:17])=[CH:8][C:7]=2[CH:30]=1

참가 물질

8

반응물 4

HCID 176Acetic AcidHCID 4207714-PiperidinemethanolHCID 5049666Sodium triacetoxyborohydrideHCID 866168355-(5-formyl-1-benzofuran-2-yl)-4-[(4-methyl-1H-indol-5-yl)amino]nicotinonitrile

생성물 2

HCID 684632525-(5-{[4-(hydroxymethyl)piperidin-1-yl]methyl}-1-benzofuran-2-yl)-4-[(4-methyl-1H-indol-5-yl)amino]nicotinonitrile수율 51%HCID 684677165-[5-(hydroxymethyl)-1-benzofuran-2-yl]-4-[(4-methyl-1H-indol-5-yl)amino]nicotinonitrile

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 13387N-methyl-2-pyrrolidone용매

실험 절차

To a suspension of 5-(5-formyl-1-benzofuran-2-yl)-4-[(4-methyl-1H-indol-5-yl)amino]nicotinonitrile (200 mg, 0.51 mmol) in a mixture of CH2Cl2 (10 mL) and NMP (1 mL) at room temperature under nitrogen was added 4-(hydroxymethyl)piperidine (176 mg, 1.53 mmol) followed by glacial acetic acid (153 mg, 2.55 mmol) and the reaction mixture was stirred at room temperature for 0.5 h. Sodium triacetoxyborohydride (540 mg, 2.55 mmol) was added in portions at 0° C. and the resulting mixture was stirred at room temperature overnight. The reaction mixture was partitioned between CH2Cl2 and saturated aqueous sodium bicarbonate, and the aqueous layer was extracted with CH2Cl2. The combined organic phases were washed with water and brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography (MeOH/CH2Cl2, 3% to 20%) to give 128 mg (51%) of 5-(5-{[4-(hydroxymethyl)piperidin-1-yl]methyl}-1-benzofuran-2-yl)-4-[(4-methyl-1H-indol-5-yl)amino]nicotinonitrile 392 as a yellow solid and 23.8 mg of 5-[5-(hydroxymethyl)-1-benzofuran-2-yl]-4-[(4-methyl-1H-indol-5-yl)amino]nicotinonitrile 481 as a yellow solid. Compound 392: HPLC retention time: 6.4 min.(g); melting range: 196-199° C.; and HRMS: 395.15023. Compound 481: HPLC retention time: 8.9 min.(g); MS: 395.3 (M+H); melting range: 232-234° C.; and HRMS: 395.15023.

후처리

  1. stirringthe resulting mixture was stirred at room temperature overnight
  2. customThe reaction mixture was partitioned between CH2Cl2 and saturated aqueous sodium bicarbonate
  3. extractionthe aqueous layer was extracted with CH2Cl2
  4. washThe combined organic phases were washed with water and brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash column chromatography (MeOH/CH2Cl2, 3% to 20%)

출처 및 근거

ORD 기록
ord-325199f22a9c43ebae9e8cbdf22d2870
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07781591B2

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