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

HRID 525739Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 525739
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]

Komponenten

5

Edukt 3

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 3776IsopropanolLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-4d845f91ee564a11bd5a986ca4fd9c7a
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09340537B2

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