Sodium Carbonate → 4-(6-quinolin-6-ylpyrazolo[1,5-c]pyrimidin-3-yl)-N-(2,2,2-trifluoro-1-pyridin-2-ylethyl)thiophene-2-carboxamide

HRID 1255864ノート

反応式

HRID 1255864 の反応式
Br[C:2]1[CH:3]=[N:4][C:5]2[N:6]([N:8]=[CH:9][C:10]=2[C:11]2[CH:12]=[C:13]([C:16]([NH:18][CH:19]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=3)[C:20]([F:23])([F:22])[F:21])=[O:17])[S:14][CH:15]=2)[CH:7]=1.[N:30]1[C:39]2[C:34](=[CH:35][C:36](B(O)O)=[CH:37][CH:38]=2)[CH:33]=[CH:32][CH:31]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.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>[N:30]1[C:39]2[C:34](=[CH:35][C:36]([N:4]3[CH:3]=[CH:2][C:7]4=[C:10]([C:11]5[CH:12]=[C:13]([C:16]([NH:18][CH:19]([C:24]6[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=6)[C:20]([F:23])([F:21])[F:22])=[O:17])[S:14][CH:15]=5)[CH:9]=[N:8][N:6]4[CH2:5]3)=[CH:37][CH:38]=2)[CH:33]=[CH:32][CH:31]=1

参加物

6

反応物 3

HCID 10340Sodium CarbonateHCID 4192671Quinolin-6-ylboronic Acid (contains varying amounts of Anhydride)HCID 687765384-(6-bromopyrazolo[1,5-a]pyrimidin-3-yl)-N-(2,2,2-trifluoro-1-pyridin-2-ylethyl) thiophene-2-carboxamide

生成物 1

HCID 687776954-(6-quinolin-6-ylpyrazolo[1,5-c]pyrimidin-3-yl)-N-(2,2,2-trifluoro-1-pyridin-2-ylethyl)thiophene-2-carboxamide

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 312751,4-Dioxane溶媒2 回

実験手順

4-(6-bromopyrazolo[1,5-a]pyrimidin-3-yl)-N-(2,2,2-trifluoro-1-pyridin-2-ylethyl)thiophene-2-carboxamide (1 eq) was mixed with quinolin-6-ylboronic acid (1.3 eq). Dioxane (10 mL) and 1M Na2CO3 (2 eq) were added. The mixture was evacuated and flushed with nitrogen under stirring, then a solution Pd(Ph3P)4 (0.05 eq) in dioxane was added under inert gas. The temperature was brought to 100° C. The reaction mixture was stirred at this temperature overnight. The reaction mixtures were filtered through Celite, and the latter was washed with methanol. Purification by reverse phase LC gave 4-(6-quinolin-6-ylpyrazolo[1,5-c]pyrimidin-3-yl)-N-(2,2,2-trifluoro-1-pyridin-2-ylethyl)thiophene-2-carboxamide. 1H NMR (400 MHz, DMSO-d6): 6.11-6.22 (1H, m), 7.47-7.52 (1H, m), 7.67 (1H, dd, J=8.3 Hz, J=4.4 Hz), 7.81 (1H, d, J=7.8 Hz), 7.93-7.98 (1H, m), 8.19 (1H, d, J=8.8 Hz), 8.32 (1H, d, J=1.2 Hz), 8.34 (1H, dd, J=8.8 Hz, J=1.95 Hz), 8.48-8.53 (1H, m), 8.59 (1H, d, J=1.95 Hz), 8.67-8.70 (1H, m), 8.72 (1H, s), 8.76 (1H, d, J=1.2 Hz), 9.00 (1H, dd, J=4.4 Hz, J=1.7 Hz), 9.26 (1H, d, J=2.2 Hz), 9.54 (1H, d, J=9.3 Hz), 9.71 (1H, d, J=2.2 Hz). LC-MS APCI: m/z 531.0 [M+H]+.

後処理

  1. customThe mixture was evacuated
  2. customflushed with nitrogen
  3. customwas brought to 100° C
  4. stirringThe reaction mixture was stirred at this temperature overnight
  5. customThe reaction mixtures
  6. filtrationwere filtered through Celite
  7. washthe latter was washed with methanol
  8. customPurification by reverse phase LC

出典と根拠

ORDレコード
ord-aaded0f405fe4bf9b420b5f1a3be100e
出典データセット
uspto-grants-2013_06
特許番号
US08461162B2

反応ノート

読み込み中…