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 446509Notes

Reaction equation

HRID 446509 reaction equation
[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

Participants

7

Reactant 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

Product 1

HCID 866634266-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-methylnicotinamideYield 85%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-8c6cd99518c748318d15ec1ebe092c7a
Source dataset
uspto-grants-2013_07
Patent number
US08476253B2

Reaction notes

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