Diisopropylethylamine → N-[((3R,4S)-1-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-4-hydroxy-3-pyrrolidinyl)methyl]-3-oxo-3,4-dihydro-2H-1,4-benzothiazine-6-sulfonamide

HRID 639120Notes

Reaction equation

HRID 639120 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].CCN(C(C)C)C(C)C.[O:33]=[C:34]1[NH:39][C:38]2[CH:40]=[C:41]([S:44](Cl)(=[O:46])=[O:45])[CH:42]=[CH:43][C:37]=2[S:36][CH2:35]1>C(Cl)Cl>[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][S:44]([C:41]3[CH:42]=[CH:43][C:37]4[S:36][CH2:35][C:34](=[O:33])[NH:39][C:38]=4[CH:40]=3)(=[O:46])=[O:45])[CH2:7]1)=[N:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 218737563-oxo-3,4-dihydro-2H-1,4-benzothiazine-6-sulfonyl chlorideHCID 59026096(3S,4S)-4-(aminomethyl)-1-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-pyrrolidinol

Product 1

HCID 59026174N-[((3R,4S)-1-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-4-hydroxy-3-pyrrolidinyl)methyl]-3-oxo-3,4-dihydro-2H-1,4-benzothiazine-6-sulfonamideYield 75.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (3S,4S)-4-(aminomethyl)-1-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-pyrrolidinol (225 mg, 0.703 mmol) in DIPEA (188 μL, 1.05 mmol) and DCM (7 mL) at 0° C. was added 3-oxo-3,4-dihydro-2H-1,4-benzothiazine-6-sulfonyl chloride (210 mg, 0.845 mmol) in one portion. The solution stirred for 0.5 h and was concentrated. The resulting residue was purified by column chromatography (silica, 2-4% MeOH in DCM (1% NH OH)) yielding the title compound (290 mg, 75%) as a white foam: LC/MS (ES) m/e 548 (M+H); H NMR (CD OD, 400 Hz) δ 8.65 (s, 1H), 8.22 (d, J=9.1 Hz, 1H), 7.53 (d, J=8.0 Hz, 1H), 7.45-7.48 (m, 2H), 7.20 (d, J=9.1 Hz, 1H), 4.28-4.31 (m, 1H), 4.14 (s, 3H), 3.55 (s, 2H), 3.42-3.46 (m, 2H), 3.21-3.23 (m, 1H), 3.05-3.15 (m, 1H), 2.91-3.05 (m, 2H), 2.86-2.90 (m, 2H), 2.51-2.62 (m, 2H), 2.33-2.4 (m, 1H).

Workup

  1. concentrationwas concentrated
  2. customThe resulting residue was purified by column chromatography (silica, 2-4% MeOH in DCM (1% NH OH))

Sources & evidence

ORD record
ord-e699368e857f476dbeab702ba9310317
Source dataset
uspto-grants-2010_04
Patent number
US07691850B2

Reaction notes

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