Pivalic acid → (R)-methyl 5-hydroxy-5-(5-(6-((4-(1-(4-methoxybenzyl)-1H-1,2,3-triazol-4-yl)pyridin-2-yl)amino)-4-methylpyridin-2-yl)thiazol-2-yl)-5,6,7,8-tetrahydronaphthalene-2-carboxylate

HRID 2402395ノート

反応式

HRID 2402395 の反応式
Br[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[C:13]([C:15]3[N:16]=[N:17][N:18]([CH2:20][C:21]4[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=4)[CH:19]=3)[CH:12]=[CH:11][N:10]=2)[CH:5]=[C:4]([CH3:29])[CH:3]=1.[OH:30][C@:31]1([C:45]2[S:46][CH:47]=[CH:48][N:49]=2)[CH2:40][CH2:39][CH2:38][C:37]2[CH:36]=[C:35]([C:41]([O:43][CH3:44])=[O:42])[CH:34]=[CH:33][C:32]1=2.C(P(C12CC3CC(CC(C3)C1)C2)C12CC3CC(CC(C3)C1)C2)CCC.[F-].[Cs+].C(O)(=O)C(C)(C)C>CC([O-])=O.CC([O-])=O.[Pd+2]>[OH:30][C@:31]1([C:45]2[S:46][C:47]([C:2]3[CH:3]=[C:4]([CH3:29])[CH:5]=[C:6]([NH:8][C:9]4[CH:14]=[C:13]([C:15]5[N:16]=[N:17][N:18]([CH2:20][C:21]6[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=6)[CH:19]=5)[CH:12]=[CH:11][N:10]=4)[N:7]=3)=[CH:48][N:49]=2)[CH2:40][CH2:39][CH2:38][C:37]2[CH:36]=[C:35]([C:41]([O:43][CH3:44])=[O:42])[CH:34]=[CH:33][C:32]1=2

参加物

7

反応物 5

HCID 6417Pivalic acidHCID 25953Cesium fluorideHCID 11371790Bis(adamantan-1-yl)(butyl)phosphaneHCID 70977548(R)-methyl 5-hydroxy-5-(thiazol-2-yl)-5,6,7,8-tetrahydronaphthalene-2-carboxylateHCID 866808016-bromo-N-(4-(1-(4-methoxybenzyl)-1H-1,2,3-triazol-4-yl)pyridin-2-yl)-4-methylpyridin-2-amine

生成物 1

HCID 86680804(R)-methyl 5-hydroxy-5-(5-(6-((4-(1-(4-methoxybenzyl)-1H-1,2,3-triazol-4-yl)pyridin-2-yl)amino)-4-methylpyridin-2-yl)thiazol-2-yl)-5,6,7,8-tetrahydronaphthalene-2-carboxylate収率 34%

試薬・触媒・溶媒 1

HCID 167845palladium(II) acetate触媒

反応条件

温度
100 °C

実験手順

To microwave vial were added 6-bromo-N-(4-(1-(4-methoxybenzyl)-1H-1,2,3-triazol-4-yl)pyridin-2-yl)-4-methylpyridin-2-amine (247 mg, 0.547 mmol), (R)-methyl 5-hydroxy-5-(thiazol-2-yl)-5,6,7,8-tetrahydronaphthalene-2-carboxylate (158 mg, 0.547 mmol), butyldi-1-adamantylphosphine (78 mg, 0.219 mmol), CsF (249 mg, 1.64 mmol), pivalic acid (95 μl, 0.821 mmol), and Pd(OAc)2 (24.6 mg, 0.109 mmol). The reaction was vacuum and purged with argon 3 times, then degassed 1,4-Dioxane (2.0 mL) was added and the reaction was heated to 100° C. for 16 h. The reaction was cooled to rt and diluted with EtOAc (20 mL). The reaction was filtered, concentrated and purified by silica gel chromatography using a gradient solvent system of 30-100% EtOAc/Hexanes. The product-containing fractions were collected and concentrated to give (R)-methyl 5-hydroxy-5-(5-(6-((4-(1-(4-methoxybenzyl)-1H-1,2,3-triazol-4-yl)pyridin-2-yl)amino)-4-methylpyridin-2-yl)thiazol-2-yl)-5,6,7,8-tetrahydronaphthalene-2-carboxylate (121 mg, 34%) as a white foam. MS ESI calcd for C36H33N7O4S [M+H]+ 660, found 660.

後処理

  1. custompurged with argon 3 times
  2. additiondegassed 1,4-Dioxane (2.0 mL) was added
  3. temperatureThe reaction was cooled to rt
  4. additiondiluted with EtOAc (20 mL)
  5. filtrationThe reaction was filtered
  6. concentrationconcentrated
  7. custompurified by silica gel chromatography
  8. customThe product-containing fractions were collected
  9. concentrationconcentrated

出典と根拠

ORDレコード
ord-ec15c21d5de543b5976318b2867e98bb
出典データセット
uspto-grants-2014_08
特許番号
US08796310B2

反応ノート

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