Sodium hydride → (S)-methyl 5-chloro-3-methyl-1-((quinuclidin-3-ylamino)methyl)-1H-indole-7-carboxylate

HRID 2168485노트

반응식

HRID 2168485 반응식
Cl.Cl.[NH2:3][C@H:4]1[CH:9]2[CH2:10][CH2:11][N:6]([CH2:7][CH2:8]2)[CH2:5]1.[H-].[Na+].[Cl:14][C:15]1[CH:16]=[C:17]2[C:21](=[C:22]([C:24]([O:26][CH3:27])=[O:25])[CH:23]=1)[N:20]([CH2:28]C=O)[CH:19]=[C:18]2[CH3:31].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.C(O)(=O)C>[Cl:14][C:15]1[CH:16]=[C:17]2[C:21](=[C:22]([C:24]([O:26][CH3:27])=[O:25])[CH:23]=1)[N:20]([CH2:28][NH:3][C@H:4]1[CH:9]3[CH2:10][CH2:11][N:6]([CH2:7][CH2:8]3)[CH2:5]1)[CH:19]=[C:18]2[CH3:31]

참가 물질

7

반응물 4

HCID 24758Sodium hydrideHCID 5049666Sodium triacetoxyborohydrideHCID 12494973(3S)-1-azabicyclo[2.2.2]octan-3-amine dihydrochlorideHCID 86672696HCID 86672696, 화합물

생성물 1

HCID 66899384(S)-methyl 5-chloro-3-methyl-1-((quinuclidin-3-ylamino)methyl)-1H-indole-7-carboxylate수율 106.3%

시약·촉매·용매 2

HCID 176Acetic Acid용매HCID 6344Dichloromethane용매

실험 절차

To a stirred suspension of (S)-(−)-3-aminoquinuclidine dihydrochloride (621 mg, 3.1 mmol) in methylene chloride (20 mL) was added sodium hydride (250 mg, 6.2 mmol) in portions and the mixture was stirred for 1 h. Acetic acid (0.6 mL) was added dropwise and then methyl 5-chloro-3-methyl-1-(2-oxoethyl)-1H-indole-7-carboxylate (690 mg, 2.6 mmol) from Step D above was added and the mixture continued to stir at room temperature for 2 h. Sodium triacetoxyborohydride (2.2 g, 10.4 mmol) was added in one portion and stirring was continued overnight at room temperature. The solvent was removed under reduced pressure and the crude material was purified by column chromatography (silica gel, 90:10:1 methylene chloride/methanol/concentrated ammonium hydroxide) to afford (S)-methyl 5-chloro-3-methyl-1-((quinuclidin-3-ylamino)methyl)-1H-indole-7-carboxylate (1.0 g, quantitative yield) as a light yellow solid: 1H NMR (500 MHz, CD3OD) δ 7.69 (d, J=1.0 Hz, 1H), 7.56 (d, J=1.0 Hz, 1H), 7.14 (s, 1H), 3.02-2.97 (m, 1H), 2.84-2.62 (m, 8H), 3.00-2.97 (m, 1H), 2.85-2.58 (m, 7H), 2.32 (s, 3H), 2.23-2.19 (dq, J=10.0, 2.0 Hz, 1H), 1.72-1.61 (m, 3H), 1.47-1.45 (m, 1H), 1.47-1.45 (m, 1H); MS (ESI+) m/z 362 (M+H).

후처리

  1. stirringto stir at room temperature for 2 h
  2. stirringstirring
  3. waitwas continued overnight at room temperature
  4. customThe solvent was removed under reduced pressure
  5. customthe crude material was purified by column chromatography (silica gel, 90:10:1 methylene chloride/methanol/concentrated ammonium hydroxide)

출처 및 근거

ORD 기록
ord-2b3407ae119f45e6917699bbcdc5e7d5
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09045501B2

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