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

HRID 525739ノート

反応式

HRID 525739 の反応式
Cl[C:2]1[C:21]([C:22]#[N:23])=[CH:20][C:5]([C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][C:16]([F:19])([F:18])[F:17])=[CH:11][CH:10]=2)=[O:7])=[CH:4][N:3]=1.[NH:24]1[CH2:28][CH2:27][C@@H:26]([OH:29])[CH2:25]1.CCN(C(C)C)C(C)C>CC(O)C>[C:22]([C:21]1[C:2]([N:24]2[CH2:28][CH2:27][C@@H:26]([OH:29])[CH2:25]2)=[N:3][CH:4]=[C:5]([CH:20]=1)[C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][C:16]([F:19])([F:18])[F:17])=[CH:11][CH:10]=1)=[O:7])#[N:23]

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 2759337(R)-3-PyrrolidinolHCID 899068936-chloro-5-cyano-N-(4-(trifluoromethoxy)phenyl)nicotinamide

生成物 1

HCID 89907102(R)-5-cyano-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

試薬・触媒・溶媒 1

HCID 3776Isopropanol溶媒

反応条件

温度
110 °C

実験手順

A stirred mixture of 6-chloro-5-cyano-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 70.3, 4.50 g, 13.2 mmol), (R)-3-Pyrrolidinol (1.38 g, 15.8 mmol) and DIPEA (3.74 g, 29.0 mmol) in iPrOH (20 mL) was heated at 110° C. for 60 min. The cooled RM was then evaporated to dryness under reduced pressure and the residue was dissolved in EtOAc, washed with sat. aq. NaHCO3 and brine. The solution was dried over anhydrous Na2SO4 and the solvent was evaporated off under reduced pressure to give a crude product which was purified by crystallization from DCM/TBME to afford the product as a colorless crystalline solid. m.p. 234-236° C., HPLC (Condition 4) tR=5.41 min, UPLC-MS (Condition 8) tR=1.01 min, m/z=393.2 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.00-1.25 (m, 1H), 1.80-2.06 (m, 1H), 3.67 (d, J=11.34 Hz, 1H), 3.82 (br. s, 3H), 4.01 (q, J=7.04 Hz, 1H), 4.40 (br. s, 1H), 7.34 (d, J=8.60 Hz, 2H), 7.83 (d, J=8.99 Hz, 2H), 8.51 (d, J=2.35 Hz, 1H), 8.83 (d, J=2.35 Hz, 1H), 10.23 (s, 1H).

後処理

  1. customThe cooled RM was then evaporated to dryness under reduced pressure
  2. dissolutionthe residue was dissolved in EtOAc
  3. washwashed with sat. aq. NaHCO3 and brine
  4. dry with materialThe solution was dried over anhydrous Na2SO4
  5. customthe solvent was evaporated off under reduced pressure
  6. customto give a crude product which
  7. customwas purified by crystallization from DCM/TBME

出典と根拠

ORDレコード
ord-4d845f91ee564a11bd5a986ca4fd9c7a
出典データセット
uspto-grants-2016_05
特許番号
US09340537B2

反応ノート

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