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 1676369ノート

反応式

HRID 1676369 の反応式
[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

参加物

8

反応物 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

生成物 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-carboxamide収率 55.4%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

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).

後処理

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

出典と根拠

ORDレコード
ord-12b2d4f226cc423099a7a359a47deaa5
出典データセット
uspto-grants-2011_08
特許番号
US08003662B2

反応ノート

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