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

HRID 525739노트

반응식

HRID 525739 반응식
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]

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 3776Isopropanol용매

반응 조건

온도
110 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-4d845f91ee564a11bd5a986ca4fd9c7a
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09340537B2

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