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Diisopropylethylamine → (R)-5-(4-Fluoro-1H-pyrazol-5-yl)-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

HRID 73739
ノート
印刷プレビュー

反応式

HRID 73739 の反応式
CCN(C(C)C)C(C)C.Cl[C:11]1[C:30]([C:31]2[NH:35][N:34]=[CH:33][C:32]=2[F:36])=[CH:29][C:14]([C:15]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][C:25]([F:28])([F:27])[F:26])=[CH:20][CH:19]=2)=[O:16])=[CH:13][N:12]=1.[NH:37]1[CH2:41][CH2:40][C@@H:39]([OH:42])[CH2:38]1>CC(O)C.CCOC(C)=O>[F:36][C:32]1[CH:33]=[N:34][NH:35][C:31]=1[C:30]1[C:11]([N:37]2[CH2:41][CH2:40][C@@H:39]([OH:42])[CH2:38]2)=[N:12][CH:13]=[C:14]([CH:29]=1)[C:15]([NH:17][C:18]1[CH:23]=[CH:22][C:21]([O:24][C:25]([F:28])([F:27])[F:26])=[CH:20][CH:19]=1)=[O:16]
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 81531DiisopropylethylamineHCID 2759337(R)-3-PyrrolidinolHCID 867026006-chloro-5-(4-fluoro-1H-pyrazol-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

生成物 1

HCID 72545355(R)-5-(4-Fluoro-1H-pyrazol-5-yl)-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

試薬・触媒・溶媒 2

HCID 3776Isopropanol溶媒
HCID 8857
Ethyl Acetate
溶媒

反応条件

温度
140 °C

実験手順

DIPEA (71.9 μL, 0.412 mmol) was added to a solution of 6-chloro-5-(4-fluoro-1H-pyrazol-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 5.1, 75 mg, 0.187 mmol) and (R)-pyrrolidin-3-ol (19.97 mg, 0.225 mmol) in iPrOH (187 μL) in a vial which was sealed and heated at 140° C. for 1 h. After cooling at RT, the RM was dissolved in EtOAc and washed with brine, dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give the crude product which was purified by flash chromatography (RediSep® Silica gel column, DCM/MeOH from 2% to 10% MeOH) to afford the title compound as a white foam. HPLC (Condition 4) tR=4.73 min, UPLC-MS (Condition 3) tR=0.93 min, m/z=452.4 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.64-1.95 (m, 2H) 3.00 (d, J=11.34 Hz, 1H) 3.18-3.51 (m, 3H) 4.22 (br. s, 1H) 4.86 (br. s, 1H) 7.32 (d, J=8.60 Hz, 2H) 7.77-8.11 (m, 4H) 8.76 (br. s, 1H) 10.17 (s, 1H) 12.90 (br. s, 1H).

後処理

  1. customwas sealed
  2. temperatureAfter cooling at RT
  3. washwashed with brine
  4. dry with materialdried over Na2SO4
  5. customthe solvent was evaporated off under reduced pressure
  6. customto give the crude product which
  7. customwas purified by flash chromatography (RediSep® Silica gel column, DCM/MeOH from 2% to 10% MeOH)

出典と根拠

ORDレコード
ord-16fdb474cc32455d817c846cd8876e84
出典データセット
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08829195B2

反応ノート

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