HCID 67019715、化合物 → HCID 86725118、化合物

HRID 634291ノート

反応式

HRID 634291 の反応式
[CH:1]([NH:4][C:5]1[O:6][C:7]([C:10]2[CH:11]=[C:12]3[C:16](=[CH:17][CH:18]=2)[N:15]([S:19]([C:22]2[CH:28]=[CH:27][C:25]([CH3:26])=[CH:24][CH:23]=2)(=[O:21])=[O:20])[CH:14]=[C:13]3B2OC(C)(C)C(C)(C)O2)=[N:8][N:9]=1)([CH3:3])[CH3:2].Br[C:39]1[S:40][C:41]([C:44]([NH:46][CH:47]2[CH2:49][CH2:48]2)=[O:45])=[CH:42][N:43]=1.ClC1SC(C(NC2CC2)=O)=CN=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[CH:47]1([NH:46][C:44]([C:41]2[S:40][C:39]([C:13]3[C:12]4[C:16](=[CH:17][CH:18]=[C:10]([C:7]5[O:6][C:5]([NH:4][CH:1]([CH3:3])[CH3:2])=[N:9][N:8]=5)[CH:11]=4)[N:15]([S:19]([C:22]4[CH:28]=[CH:27][C:25]([CH3:26])=[CH:24][CH:23]=4)(=[O:20])=[O:21])[CH:14]=3)=[N:43][CH:42]=2)=[O:45])[CH2:48][CH2:49]1

参加物

6

反応物 3

HCID 67019715HCID 67019715、化合物HCID 68328139HCID 68328139、化合物HCID 68328163HCID 68328163、化合物

生成物 1

HCID 86725118HCID 86725118、化合物収率 75%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒

反応条件

温度
130 °C

実験手順

A mixture of N-isopropyl-5-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazol-2-amine (150 mg, 0.287 mmol), 78 mg of the 1:1 mixture of 2-bromo-N-cyclopropylthiazole-5-carboxamide and 2-chloro-N-cyclopropylthiazole-5-carboxamide, Pd2(dba)3 (Strem Chemicals, 8 mg, 8.6 μmol), Xphos (Stem Chemicals, cat #15-1152, 9 mg, 17 μmol), potassium phosphate (183 mg, 0.861 mmol) in dioxane (2.5 mL) and water (0.5 mL) was heated in an Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 130° C. for 25 min. LCMS indicated the presence of desired product (M+1=563.0), as well as a significant amount of the starting N-isopropyl-5-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazol-2-amine. To the reaction mixture was added Pd(PPh3)4 (Strem Chemicals, cat #46-2150, 10 mg) and 50 mg of the 1:1 mixture of 2-bromo-N-cyclopropylthiazole-5-carboxamide and 2-chloro-N-cyclopropylthiazole-5-carboxamide. It was heated again at 130° C. for 15 min in an Initiator microwave reactor. The reaction mixture was treated with water (5 mL) and extracted with EtOAc (2×25 mL). The organic extracts were washed with brine, dried over MgSO4, filtered and concentrated. The crude material was purified by silica gel flash chromatography using a gradient of 20-100% EtOAc in hexanes to give N-cyclopropyl-2-(5-(5-(isopropylamino)-1,3,4-oxadiazol-2-yl)-1-tosyl-1H-indol-3-yl)thiazole-5-carb oxamide (60 mg, in 75% purity) as a brown amorphous solid. MS (ESI, pos. ion) m/z: 563.0 (M+1).

後処理

  1. additionTo the reaction mixture was added
  2. extractionextracted with EtOAc (2×25 mL)
  3. washThe organic extracts were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by silica gel flash chromatography

出典と根拠

ORDレコード
ord-d74592c715e7439db335af29415079e7
出典データセット
uspto-grants-2016_04
特許番号
US09321756B2

反応ノート

読み込み中…