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 639113노트

반응식

HRID 639113 반응식
[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

참가 물질

7

반응물 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, 화합물

생성물 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-carboxamide수율 17.8%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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)+.

후처리

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

출처 및 근거

ORD 기록
ord-2b8eecbb89a347e394d66d95ebb0e64c
출처 데이터셋
uspto-grants-2010_04
특허 번호
US07691850B2

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