Diisopropylethylamine → 6-chloro-2-fluoro-N-(3-methoxy-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-5-yl)-3-(3-(4-methoxyphenoxy)propylsulfonamido)benzamide

HRID 1943951ノート

反応式

HRID 1943951 の反応式
[CH3:1][O:2][C:3]1[C:11]2[C:6](=[N:7][CH:8]=[C:9]([NH2:12])[CH:10]=2)[N:5]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)[N:4]=1.[Cl:22][C:23]1[C:28]([C:29](O)=[O:30])=[C:27]([F:32])[C:26]([NH:33][S:34]([CH2:37][CH2:38][CH2:39][O:40][C:41]2[CH:46]=[CH:45][C:44]([O:47][CH3:48])=[CH:43][CH:42]=2)(=[O:36])=[O:35])=[CH:25][CH:24]=1.Cl.C(N=C=NCCCN(C)C)C.O.N1(O)C2C=CC=CC=2N=N1.C(N(C(C)C)C(C)C)C>C(Cl)Cl>[Cl:22][C:23]1[C:28]([C:29]([NH:12][C:9]2[CH:10]=[C:11]3[C:3]([O:2][CH3:1])=[N:4][N:5]([CH2:13][C:14]4[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=4)[C:6]3=[N:7][CH:8]=2)=[O:30])=[C:27]([F:32])[C:26]([NH:33][S:34]([CH2:37][CH2:38][CH2:39][O:40][C:41]2[CH:42]=[CH:43][C:44]([O:47][CH3:48])=[CH:45][CH:46]=2)(=[O:36])=[O:35])=[CH:25][CH:24]=1

参加物

7

反応物 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 670888713-Methoxy-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-5-amineHCID 670890016-Chloro-2-fluoro-3-(3-(4-methoxyphenoxy)propylsulfonamido)benzoic acid

生成物 1

HCID 670888896-chloro-2-fluoro-N-(3-methoxy-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-5-yl)-3-(3-(4-methoxyphenoxy)propylsulfonamido)benzamide収率 77.6%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

A 100 mL, round-bottomed flask was charged with 3-methoxy-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-5-amine (123.0 mg, 0.43 mmol), 6-chloro-2-fluoro-3-(3-(4-methoxyphenoxy)propylsulfonamido)benzoic acid (271.1 mg, 0.65 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (124.4 mg, 0.65 mmol), 1H-benzo[d][1,2,3]triazol-1-ol hydrate (99.4 mg, 0.65 mmol), N-ethyl-N-isopropylpropan-2-amine (83.9 mg, 0.65 mmol) and DCM (1.5 mL). The reaction mixture was stirred at room temperature until LC-MS showed that the starting material had been consumed (about 12 hours). Then the reaction mixture was partitioned between EtOAc (300 mL) and water (150 mL). The phases were separated, and the aqueous phase was extracted with EtOAc (3×150 mL). The combined organic layers were dried (Na2SO4), filtered and concentrated to yield a crude product. The crude product was purified by silica gel chromatography (EtOAc/hexane from 1/4 to 1/0, v/v) to afford 6-chloro-2-fluoro-N-(3-methoxy-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-5-yl)-3-(3-(4-methoxyphenoxy)propylsulfonamido)benzamide (228.3 mg, 77.14%). LRMS (APCI pos): >95% purity, 254 nm, m/e 684.1 and 686.2 (M+1).

後処理

  1. customhad been consumed (about 12 hours)
  2. customThen the reaction mixture was partitioned between EtOAc (300 mL) and water (150 mL)
  3. customThe phases were separated
  4. extractionthe aqueous phase was extracted with EtOAc (3×150 mL)
  5. dry with materialThe combined organic layers were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto yield a crude product
  9. customThe crude product was purified by silica gel chromatography (EtOAc/hexane from 1/4 to 1/0

出典と根拠

ORDレコード
ord-16d1d7352cc04436bc75e622edf56129
出典データセット
uspto-grants-2013_03
特許番号
US08394795B2

反応ノート

読み込み中…