2-Chloro-4-[(5-fluoroquinazolin-4-yl)amino]phenol → 4-[(5-{(1R)-2-[allyl(methyl)amino]-1-methylethoxy}quinazolin-4-yl)amino]-2-chlorophenol

HRID 1864198Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1864198
[Cl:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][C:17]=3F)[N:12]=[CH:11][N:10]=2)[CH:5]=[CH:4][C:3]=1[OH:20].[CH2:21]([N:24]([CH3:29])[CH2:25][C@H:26]([OH:28])[CH3:27])[CH:22]=[CH2:23]>CC(N(C)C)=O.[H-].[Na+]>[CH2:21]([N:24]([CH3:29])[CH2:25][C@@H:26]([CH3:27])[O:28][C:17]1[CH:16]=[CH:15][CH:14]=[C:13]2[C:18]=1[C:9]([NH:8][C:6]1[CH:5]=[CH:4][C:3]([OH:20])=[C:2]([Cl:1])[CH:7]=1)=[N:10][CH:11]=[N:12]2)[CH:22]=[CH2:23]

Komponenten

5

Edukt 2

HCID 574449782-Chloro-4-[(5-fluoroquinazolin-4-yl)amino]phenolHCID 86615686(2R)-1-[allyl(methyl)amino]propan-2-ol

Produkt 1

HCID 690577904-[(5-{(1R)-2-[allyl(methyl)amino]-1-methylethoxy}quinazolin-4-yl)amino]-2-chlorophenolAusbeute 68,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 24758Sodium hydrideLösungsmittelHCID 31374DimethylacetamideLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

2-chloro-4-[(5-fluoroquinazolin-4-yl)amino]phenol (2 g) was added to a stirred solution of (2R)-1-[allyl(methyl)amino]propan-2-ol (2.24 g, prepared as described in Example 2-3) in DMA (100 ml) and sodium hydride (60% dispersion in oil, 692 mg), and the mixture heated to 110° C. for 16 hours. The mixture was concentrated in vacuo then a saturated solution of sodium bicarbonate (200 ml) was added and extracted with DCM (300 ml). The extract washed with brine, dried and concentrated in vacuo and the residue purified by chromatography using DCM—10% methanol/2N ammonia as eluent to give 4-[(5-{(1R)-2-[allyl(methyl)amino]-1-methylethoxy}quinazolin-4-yl)amino]-2-chlorophenol as a yellow solid (1.88 g, 68%); NMR spectrum (DMSO-d6) 1.43 (d, 3H), 2.17 (s, 3H), 2.54 (dd, 1H), 2.97 (m, 3H), 4.94 (m, 1H), 5.00 (dd, 1H), 5.10 (dd, 1H), 5.63 (m, 1H), 6.98 (d, 1H), 7.18 (d, 1H), 7.29 (d, 1H), 7.42 (dd, 1H), 7.69 (t, 1H), 7.84 (d, 1H), 8.44 (s, 1H), 10.01 (bs, 1H), 10.26 (s, 1H); Mass spectrum MH+ 399.

Aufarbeitung

  1. concentrationThe mixture was concentrated in vacuo
  2. additiona saturated solution of sodium bicarbonate (200 ml) was added
  3. extractionextracted with DCM (300 ml)
  4. washThe extract washed with brine
  5. customdried
  6. concentrationconcentrated in vacuo
  7. customthe residue purified by chromatography

Quellen und Nachweise

ORD-Eintrag
ord-693ed1feb24c4e58adf295846318263f
Quelldatensatz
uspto-grants-2009_12
Patentnummer
US07625908B2

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