1,2-Dichloroethane → N-[((3S,4S)-1-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-4-hydroxy-3-pyrrolidinyl)methyl]-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-6-carboxamide

HRID 639121Notes

Reaction equation

HRID 639121 reaction equation
[NH2:1][CH2:2][C@H:3]1[CH2:7][N:6]([CH2:8][CH2:9][C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH3:21])[N:18]=3)[N:13]=[CH:12][C:11]=2[F:22])[CH2:5][C@H:4]1[OH:23].[O:24]=[C:25]1[CH2:30][O:29][C:28]2[CH:31]=[CH:32][C:33]([C:35](O)=[O:36])=[N:34][C:27]=2[NH:26]1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>C(Cl)Cl.CN(C=O)C>[F:22][C:11]1[CH:12]=[N:13][C:14]2[C:19]([C:10]=1[CH2:9][CH2:8][N:6]1[CH2:5][C@@H:4]([OH:23])[C@@H:3]([CH2:2][NH:1][C:35]([C:33]3[CH:32]=[CH:31][C:28]4[O:29][CH2:30][C:25](=[O:24])[NH:26][C:27]=4[N:34]=3)=[O:36])[CH2:7]1)=[N:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 574231133-Oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-6-carboxylic acidHCID 59026096(3S,4S)-4-(aminomethyl)-1-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-pyrrolidinol

Product 1

HCID 11605675N-[((3S,4S)-1-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-4-hydroxy-3-pyrrolidinyl)methyl]-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-6-carboxamideYield 36.4%

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

To a solution of (3S,4S)-4-(aminomethyl)-1-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-pyrrolidinol (230 mg, 0.719 mmol) in DCM-DMF (6:1, 7 mL) at 25° C. were added 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-6-carboxylic acid (140 mg, 0.719 mmol), EDC (134 mg, 0.836 mmol) and HOBT (117 mg, 0.863 mmol). After 12 h, the solution was concentrated and purified by column chromatography (silica, 2-3% MeOH in DCM (1% NH OH)) yielding the title compound (130 mg, 36%) as a yellow foam: LC/MS (ES) m/e 497 (M+H); H NMR (CD OD, 400 Hz) δ 8.4 (s, 1H), 7.95 (d, J=9.1 Hz, 1H), 7.53 (d, J=8.2 Hz, 1H), 7.19 (d, J=8.2 Hz, 1H), 6.93 (d, J=9.1 Hz, 1H), 4.63 (AB quart., 2H), 4.20-4.24 (m, 1H), 3.9 (s, 3H), 3.55-3.59 (m, 1H), 3.40-3.43 (m, 1H), 3.23-3.28 (m, 2H), 3.16-3.19 (m, 1H), 2.91-2.94 (m, 1H), 2.7-2.82 (m, 2H), 2.49-2.52 (m, 2H), 2.37-2.42 (m, 1H).

Workup

  1. concentrationthe solution was concentrated
  2. custompurified by column chromatography (silica, 2-3% MeOH in DCM (1% NH OH))

Sources & evidence

ORD record
ord-5d07797205f94271a817f25858ca8494
Source dataset
uspto-grants-2010_04
Patent number
US07691850B2

Reaction notes

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