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

HRID 639113Notes

Reaction equation

HRID 639113 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]1O.C(N(C(C)C)CC)(C)C.[O:33]=[C:34]1[CH2:39][S:38][C:37]2[CH:40]=[CH:41][C:42]([C:44](O)=[O:45])=[N:43][C:36]=2[NH:35]1.O.OC1C2N=NNC=2C=CC=1.C(Cl)CCl>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][CH2:4][C@@H:3]([CH2:2][NH:1][C:44]([C:42]3[CH:41]=[CH:40][C:37]4[S:38][CH2:39][C:34](=[O:33])[NH:35][C:36]=4[N:43]=3)=[O:45])[CH2:7]1)=[N:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 218737873-Oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carboxylic acidHCID 59026096(3S,4S)-4-(aminomethyl)-1-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-pyrrolidinolHCID 178526939HCID 178526939, compound

Product 1

HCID 11720215N-[((3S)-1-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-pyrrolidinyl)methyl]-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carboxamideYield 17.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of (3S,4S)-4-(aminomethyl)-1-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-pyrrolidinol (105 mg, 0.34 mmole) in dry in DMF (25 mL) at RT was added diisopropylethylamine (0.18 mL, 1.02 mmole), 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carboxylic acid (0.93 mg, 0.44 mmole), hydroxybenzotriazole hydrate (51 mg, 0.38 mmole) and EDC (73 mg, 0.38 mmole). After 18 h, the reaction contents were concentrated under high vacuum. Purification on silica (CHCl3/MeOH, 9:1 containing 5% NH4OH) afforded the title compound (30 mg, 17%) as a light yellow solid: 1H NMR (400 MHz, CD3OD) δ 8.62 (m, 1H), 8.56 (s, 1H), 8.16 (d, J=9.04 Hz, 1H), 7.99 (m, 1H), 7.83 (d, J=7.91 Hz, 1H), 7.76 (d, J=7.92 Hz, 1H), 7.05 (d, J=9.04 Hz, 1H), 4.07 (s, 3H), 3.53 (d, 2H), 2.43-3.51 (br m, 11H), 2.06 (m, 1H), 1.58 (m, 1H). LC-MS (ES) m/e 497 (M+H)+.

Workup

  1. customthe reaction contents
  2. concentrationwere concentrated under high vacuum
  3. customPurification on silica (CHCl3/MeOH, 9:1 containing 5% NH4OH)

Sources & evidence

ORD record
ord-2b8eecbb89a347e394d66d95ebb0e64c
Source dataset
uspto-grants-2010_04
Patent number
US07691850B2

Reaction notes

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