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 639113ノート

反応式

HRID 639113 の反応式
[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

参加物

7

反応物 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、化合物

生成物 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-carboxamide収率 17.8%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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)+.

後処理

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

出典と根拠

ORDレコード
ord-2b8eecbb89a347e394d66d95ebb0e64c
出典データセット
uspto-grants-2010_04
特許番号
US07691850B2

反応ノート

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