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Sodium Bicarbonate → tert-butyl 4-(4-(6-amino-5-(1-(2,3-difluoro-4-methoxyphenyl)-1H-tetrazol-5-yl)pyridin-3-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate

HRID 446744
ノート
印刷プレビュー

反応式

HRID 446744 の反応式
Br[C:2]1[CH:3]=[C:4]([C:9]2[N:13]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([F:22])[C:15]=3[F:23])[N:12]=[N:11][N:10]=2)[C:5]([NH2:8])=[N:6][CH:7]=1.CC1(C)C(C)(C)OB([C:32]2[CH:33]=[N:34][N:35]([CH:37]3[CH2:42][CH2:41][N:40]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:39][CH2:38]3)[CH:36]=2)O1.C(=O)(O)[O-].[Na+]>Cl[Pd]Cl.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].COCCOC>[NH2:8][C:5]1[N:6]=[CH:7][C:2]([C:32]2[CH:33]=[N:34][N:35]([CH:37]3[CH2:38][CH2:39][N:40]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:41][CH2:42]3)[CH:36]=2)=[CH:3][C:4]=1[C:9]1[N:13]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([F:22])[C:15]=2[F:23])[N:12]=[N:11][N:10]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 516892Sodium BicarbonateHCID 45480279tert-butyl 4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylate2 回HCID 582937635-bromo-3-(1-(2,3-difluoro-4-methoxyphenyl)-1H-tetrazol-5-yl)pyridin-2-amine2 回

生成物 1

HCID 58293836tert-butyl 4-(4-(6-amino-5-(1-(2,3-difluoro-4-methoxyphenyl)-1H-tetrazol-5-yl)pyridin-3-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate収率 50.6%

試薬・触媒・溶媒 2

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
70 °C

実験手順

To a round-bottom flask charged with 5-bromo-3-(1-(2,3-difluoro-4-methoxyphenyl)-1H-tetrazol-5-yl)pyridin-2-amine (Compound 1078, 3.832 g, 10 mmol), tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (Compound 1098, 4.150 g, 11.00 mmol) and DME (100 mL) was flushed with N2 for 20 min. An aqueous solution of sodium bicarbonate (25 mL of 1.2 M, 30.00 mmol) was added. Nitrogen flow was continued for another 40 min before the addition of PdCl2 dppf (731.7 mg, 1.00 mmol). The resulting suspension was heated at 70° C. for 15 hours, filtered though a layer of diatomaceous earth, and washed with brine. The volatiles were removed in vacuo to afford a residue, which was purified by silica gel chromatography, eluting with 20-100% EtOAc/hexanes to yield tert-butyl 4-(4-(6-amino-5-(1-(2,3-difluoro-4-methoxyphenyl)-1H-tetrazol-5-yl)pyridin-3-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (Compound 1103, 2.8 g, 50.6%) as yellow solid; ESMS (M+H)=554.

後処理

  1. customwas flushed with N2 for 20 min
  2. filtrationfiltered though a layer of diatomaceous earth
  3. washwashed with brine
  4. customThe volatiles were removed in vacuo
  5. customto afford a residue, which
  6. customwas purified by silica gel chromatography
  7. washeluting with 20-100% EtOAc/hexanes

出典と根拠

ORDレコード
ord-35eccede60fc4900b4e728b3a9709e64
出典データセット
uspto-grants-2013_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08481524B2

反応ノート

読み込み中…

このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート