Diisopropylethylamine → (S)-5-bromo-6-(3-(hydroxymethyl)pyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

HRID 73743

反応式

HRID 73743 の反応式
[Br:1][C:2]1[C:3](Cl)=[N:4][CH:5]=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8].C1CNC([CH2:28][OH:29])C1.Cl.CC[N:33]([CH:37]([CH3:39])C)[CH:34]([CH3:36])C>CC(O)C>[Br:1][C:2]1[C:3]([N:33]2[CH2:34][CH2:36][C@H:39]([CH2:28][OH:29])[CH2:37]2)=[N:4][CH:5]=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8]

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 17802800Pyrrolidin-2-ylmethanol hydrochlorideHCID 867025955-bromo-6-chloro-N-(4-(trifluoromethoxy)phenyl)nicotinamide

生成物 1

HCID 86702601(S)-5-bromo-6-(3-(hydroxymethyl)pyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

試薬・触媒・溶媒 1

HCID 3776Isopropanol溶媒

実験手順

A mixture of 5-bromo-6-chloro-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 2.3, 500 mg, 1.264 mmol), (S)-beta-prolinol hydrochloride (226 mg, 1.643 mmol), DIPEA (662 μL, 3.79 mmol) and iPrOH (1.945 mL) in a sealed vial was subjected to MW irradiation at 140° C. for 60 min. The solvent was evaporated off under reduced pressure and the residue was treated with aq. 0.5 M HCl (20 mL) and extracted with EtOAc. The combined extracts were washed with 0.5 M HCl (10 ml) and water, dried over MgSO4 and the solvent was evaporated off under reduced pressure to give the product which was triturated with cyclohexane, filtered and dried to afford the title compound as a white solid. UPLC-MS (Condition 1) tR=2.76 min, m/z=460.0/462.0 [M+H]+, m/z=458.0/460.0 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.59-1.76 (m, 1H) 1.92-2.04 (m, 1H) 2.26-2.44 (m, 1H) 3.37-3.50 (m, 2H) 3.56 (dd, J=11.00, 7.34 Hz, 1H) 3.67-3.85 (m, 3H) 4.71 (br. s, 1H) 7.35 (d, J=8.56 Hz, 2H) 7.85 (d, 1H) 8.34 (d, J=1.96 Hz, 1H) 8.68 (d, J=1.96 Hz, 1H) 10.21 (s, 1H).

後処理

  1. customvial was subjected to MW irradiation at 140° C. for 60 min
  2. customThe solvent was evaporated off under reduced pressure
  3. additionthe residue was treated with aq. 0.5 M HCl (20 mL)
  4. extractionextracted with EtOAc
  5. washThe combined extracts were washed with 0.5 M HCl (10 ml) and water
  6. dry with materialdried over MgSO4
  7. customthe solvent was evaporated off under reduced pressure
  8. customto give the product which
  9. customwas triturated with cyclohexane
  10. filtrationfiltered
  11. customdried

出典と根拠

ORDレコード
ord-507b5407677f4b4d8805321432fda126
出典データセット
uspto-grants-2014_09
特許番号
US08829195B2

関連ノート

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