1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (R)-N-(3-fluoro-4-(2-(4-(3-hydroxypyrrolidine-1-carbonyl)phenyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide

HRID 1676369노트

반응식

HRID 1676369 반응식
[F:1][C:2]1[CH:26]=[C:25]([NH:27][C:28]([C:30]2[C:35](=[O:36])[N:34]([C:37]3[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=3)[N:33]=[CH:32][CH:31]=2)=[O:29])[CH:24]=[CH:23][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]2[CH:11]=[C:12]([C:14]3[CH:22]=[CH:21][C:17]([C:18]([OH:20])=O)=[CH:16][CH:15]=3)[S:13][C:6]=12.C1C=CC2N(O)N=NC=2C=1.O.CCN=C=NCCCN(C)C.[NH:66]1[CH2:70][CH2:69][C@@H:68]([OH:71])[CH2:67]1.CCN(C(C)C)C(C)C>O.CN(C=O)C>[F:1][C:2]1[CH:26]=[C:25]([NH:27][C:28]([C:30]2[C:35](=[O:36])[N:34]([C:37]3[CH:38]=[CH:39][C:40]([F:43])=[CH:41][CH:42]=3)[N:33]=[CH:32][CH:31]=2)=[O:29])[CH:24]=[CH:23][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]2[CH:11]=[C:12]([C:14]3[CH:15]=[CH:16][C:17]([C:18]([N:66]4[CH2:70][CH2:69][C@@H:68]([OH:71])[CH2:67]4)=[O:20])=[CH:21][CH:22]=3)[S:13][C:6]=12

참가 물질

8

반응물 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 2759337(R)-3-PyrrolidinolHCID 27960291-Hydroxybenzotriazole hydrateHCID 673452974-(7-(2-Fluoro-4-(1-(4-fluorophenyl)-6-oxo-1,6-dihydropyridazine-5-carboxamido)phenoxy)thieno[3,2-b]pyridin-2-yl)benzoic acid

생성물 1

HCID 58949446(R)-N-(3-fluoro-4-(2-(4-(3-hydroxypyrrolidine-1-carbonyl)phenyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide수율 55.4%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

A capped vial was charged with 4-(7-(2-fluoro-4-(1-(4-fluorophenyl)-6-oxo-1,6-dihydropyridazine-5-carboxamido)phenoxy)thieno[3,2-b]pyridin-2-yl)benzoic acid (0.100 g, 0.168 mmol), HOBT-H2O (0.103 g, 0.671 mmol), EDCI (0.129 g, 0.671 mmol), and DMF (2 mL). After stirring for 45 minutes, (R)-pyrrolidin-3-ol (0.0584 g, 0.671 mmol) and Hunig's base (0.175 ml, 1.01 mmol) were added. After stirring for 18 hours, water (20 mL) was added. The formed precipitate was isolated by filtration. After drying, (62 mg, 55%) of product was isolated as orange solid. LRMS (esi+) 666 m/z (M+1) detected. 1H NMR (CDCl3, 400 MHz) δ 11.84 (s, 1H), 8.47 (s, 1H), 8.39 (d, J=4 Hz, 1H), 8.22 (d, J=4 Hz, 1H), 7.97 (m, 1H), 7.76 (m, 3H), 7.62 (m, 4H), 7.39 (d, J=9 Hz, 1H), 7.26 (m, 3H), 6.52 (d, J=6 Hz, 1H), 4.50 (br s, 1H), 3.72 (m, 5H), 2.07 (m, 2H).

후처리

  1. stirringAfter stirring for 18 hours
  2. customThe formed precipitate was isolated by filtration
  3. customAfter drying

출처 및 근거

ORD 기록
ord-12b2d4f226cc423099a7a359a47deaa5
출처 데이터셋
uspto-grants-2011_08
특허 번호
US08003662B2

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