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6-Aminonicotinic acid → 6-Amino-N-{3-[({[(2S)-1'-{2-[(5R)-3-[3,5-bis(trifluoromethyl)benzoyl]-5-(4-fluorophenyl)-1,3-oxazolidin-5-yl]ethyl}-2,3-dihydrospiro[indene-1,4'-piperidin]-2-yl]oxy}acetyl)(methyl)amino]propyl}-N-methylnicotinamide

HRID 446509
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HRID 446509 반응식
[F:1][C:2]([F:55])([F:54])[C:3]1[CH:4]=[C:5]([CH:47]=[C:48]([C:50]([F:53])([F:52])[F:51])[CH:49]=1)[C:6]([N:8]1[CH2:12][C@@:11]([CH2:20][CH2:21][N:22]2[CH2:27][CH2:26][C:25]3([C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[CH2:29][C@@H:28]3[O:36][CH2:37][C:38]([N:40]([CH3:46])[CH2:41][CH2:42][CH2:43][NH:44][CH3:45])=[O:39])[CH2:24][CH2:23]2)([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)[O:10][CH2:9]1)=[O:7].[NH2:56][C:57]1[N:62]=[CH:61][C:60]([C:63]([OH:65])=O)=[CH:59][CH:58]=1.Cl.C(N=C=NCCCN(C)C)C>C(Cl)Cl.CN(C)C=O.CN(C)C1C=CN=CC=1>[NH2:56][C:57]1[CH:58]=[CH:59][C:60]([C:63]([N:44]([CH2:43][CH2:42][CH2:41][N:40]([C:38](=[O:39])[CH2:37][O:36][C@@H:28]2[C:25]3([CH2:26][CH2:27][N:22]([CH2:21][CH2:20][C@:11]4([C:13]5[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=5)[O:10][CH2:9][N:8]([C:6](=[O:7])[C:5]5[CH:47]=[C:48]([C:50]([F:51])([F:52])[F:53])[CH:49]=[C:3]([C:2]([F:54])([F:1])[F:55])[CH:4]=5)[CH2:12]4)[CH2:23][CH2:24]3)[C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[CH2:29]2)[CH3:46])[CH3:45])=[O:65])=[CH:61][N:62]=1
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참가 물질

7

반응물 3

HCID 184966-Aminonicotinic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 866634192-{[(2S)-1'-{2-[(5R)-3-[3,5-Bis(trifluoromethyl)benzoyl]-5-(4-fluorophenyl)-1,3-oxazolidin-5-yl]ethyl}-2,3-dihydrospiro[indene-1,4'-piperidin]-2-yl]oxy}-N-methyl-N-[3-(methylamino)propyl]acetamide

생성물 1

HCID 86663426
6-Amino-N-{3-[({[(2S)-1'-{2-[(5R)-3-[3,5-bis(trifluoromethyl)benzoyl]-5-(4-fluorophenyl)-1,3-oxazolidin-5-yl]ethyl}-2,3-dihydrospiro[indene-1,4'-piperidin]-2-yl]oxy}acetyl)(methyl)amino]propyl}-N-methylnicotinamide
수율 85%

시약·촉매·용매 3

HCID 142844-(Dimethylamino)pyridine촉매HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

실험 절차

The compound (200 mg, 0.257 mmol) obtained in Example 1k was dissolved in methylene chloride (3 mL)-N,N-dimethylformamide (2 mL), 6-aminopyridine-3-carboxylic acid (36 mg, 0.257 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (74 mg, 0.386 mmol) and 4-dimethylaminopyridine (4 mg, 0.0258 mmol) were added, and the mixture was stirred overnight at room temperature. The solvent was evaporated under reduced pressure, and the resulting residue was purified by NH silica gel column chromatography (ethyl acetate:methanol=40:1, v/v) to give the title compound (196 mg; yield, 85%) as a white solid.

후처리

  1. additionwere added
  2. customThe solvent was evaporated under reduced pressure
  3. customthe resulting residue was purified by NH silica gel column chromatography (ethyl acetate

출처 및 근거

ORD 기록
ord-8c6cd99518c748318d15ec1ebe092c7a
출처 데이터셋
uspto-grants-2013_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08476253B2

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