Methanesulfonyl chloride → Methanesulfonic acid 2-{3-[5-(3-{(1S,4R)-4-[3-(4-aza-spiro[2.5]oct-4-yl)-[1,2,4] triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureido)-3-tert-butyl-pyrazol-1-yl]-phenoxy}-ethyl ester

HRID 630957ノート

反応式

HRID 630957 の反応式
[CH2:1]1[C:3]2([CH2:8][CH2:7][CH2:6][CH2:5][N:4]2[C:9]2[N:13]3[CH:14]=[C:15]([O:18][C@H:19]4[C:28]5[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=5)[C@@H:22]([NH:29][C:30]([NH:32][C:33]5[N:34]([C:42]6[CH:47]=[CH:46][CH:45]=[C:44]([O:48][CH2:49][CH2:50][OH:51])[CH:43]=6)[N:35]=[C:36]([C:38]([CH3:41])([CH3:40])[CH3:39])[CH:37]=5)=[O:31])[CH2:21][CH2:20]4)[CH:16]=[CH:17][C:12]3=[N:11][N:10]=2)[CH2:2]1.CCN(C(C)C)C(C)C.[CH3:61][S:62](Cl)(=[O:64])=[O:63].C([O-])(O)=O.[Na+]>C(Cl)Cl.O>[CH2:2]1[C:3]2([CH2:8][CH2:7][CH2:6][CH2:5][N:4]2[C:9]2[N:13]3[CH:14]=[C:15]([O:18][C@H:19]4[C:28]5[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=5)[C@@H:22]([NH:29][C:30](=[O:31])[NH:32][C:33]5[N:34]([C:42]6[CH:43]=[C:44]([CH:45]=[CH:46][CH:47]=6)[O:48][CH2:49][CH2:50][O:51][S:62]([CH3:61])(=[O:64])=[O:63])[N:35]=[C:36]([C:38]([CH3:41])([CH3:39])[CH3:40])[CH:37]=5)[CH2:21][CH2:20]4)[CH:16]=[CH:17][C:12]3=[N:11][N:10]=2)[CH2:1]1

参加物

7

反応物 4

HCID 31297Methanesulfonyl chloride2 回HCID 81531Diisopropylethylamine2 回HCID 516892Sodium BicarbonateHCID 866872671-{(1S,4R)-4-[3-(4-Aza-spiro[2.5]oct-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-3-{5-tert-butyl-2-[3-(2-hydroxy-ethoxy)-phenyl]-2H-pyrazol-3-yl}-urea

生成物 1

HCID 86687268Methanesulfonic acid 2-{3-[5-(3-{(1S,4R)-4-[3-(4-aza-spiro[2.5]oct-4-yl)-[1,2,4] triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureido)-3-tert-butyl-pyrazol-1-yl]-phenoxy}-ethyl ester収率 100%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6344Dichloromethane溶媒

実験手順

A yellow-orange solution of Intermediate 148f (137 mg, 0.198 mmol), DIPEA (0.10 mL, 0.60 mmol) and methanesulfonyl chloride (45 mg, 0.40 mmol) in DCM (5 mL) was stirred at 0° C. for 30 min, and at RT for 30 min. DIPEA (0.052 mL, 0.30 mmol) and MsCl (23 mg, 0.20 mmol) were added and the solution stirred at RT for 30 min. Water (2 mL) and sat. aq. NaHCO3 solution (2 mL) were added and the mixture shaken. The aqueous was extracted with DCM (5 mL), then the combined organics passed through a hydrophobic frit and concentrated in vacuo to leave the title compound as a yellow solid (100%). LCMS (Method 3): Rt 3.80 min, m/z 769 [MH+].

後処理

  1. stirringthe mixture shaken
  2. extractionThe aqueous was extracted with DCM (5 mL)
  3. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-9def68377ad44ac2bdcb958bab3ea450
出典データセット
uspto-grants-2016_04
特許番号
US09315503B2

反応ノート

読み込み中…