Triphenylphosphine → methyl (2R)-2-[(4-{[1-(pyridin-2-ylmethyl)-1H-indazol-5-yl]amino}quinazolin-5-yl)oxy]propanoate

HRID 1162202Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1162202
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][N:8]1[C:16]2[C:11](=[CH:12][C:13]([NH:17][C:18]3[C:27]4[C:26]([OH:28])=[CH:25][CH:24]=[CH:23][C:22]=4[N:21]=[CH:20][N:19]=3)=[CH:14][CH:15]=2)[CH:10]=[N:9]1.O[C@@H:30]([CH3:35])[C:31]([O:33][CH3:34])=[O:32].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][N:8]1[C:16]2[C:11](=[CH:12][C:13]([NH:17][C:18]3[C:27]4[C:22](=[CH:23][CH:24]=[CH:25][C:26]=4[O:28][C@H:30]([CH3:35])[C:31]([O:33][CH3:34])=[O:32])[N:21]=[CH:20][N:19]=3)=[CH:14][CH:15]=2)[CH:10]=[N:9]1

Komponenten

5

Edukt 3

HCID 11776TriphenylphosphineHCID 94386methyl (S)-lactateHCID 1363467194-{[1-(pyridin-2-ylmethyl)-1H-indazol-5-yl]amino}quinazolin-5-ol

Produkt 1

HCID 86627834methyl (2R)-2-[(4-{[1-(pyridin-2-ylmethyl)-1H-indazol-5-yl]amino}quinazolin-5-yl)oxy]propanoateAusbeute 74 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a stirred partial solution of 4-{[1-(pyridin-2-ylmethyl)-1H-indazol-5-yl]amino}quinazolin-5-ol (870 mg, 2.36 mmol), methyl (2S)-2-hydroxypropanoate (368 mg, 3.54 mmol) and triphenylphosphine (927 mg, 3.54 mmol) in DCM (20 ml) was added DTAD (814 mg, 3.54 mmol). The mixture was stirred for 1 hour, becoming a clear solution. The solution was extracted with 2N aqueous hydrogen chloride, discarding the organic phase. The aqueous phase was basified with aqueous ammonia and extracted with DCM. The organic phase was washed with brine, dried and evaporated to an oil which crystallised on trituration with ether to give methyl (2R)-2-[(4-{[1-(pyridin-2-ylmethyl)-1H-indazol-5-yl]amino}quinazolin-5-yl)oxy]propanoate (789 mg, 74%); NMR spectrum (300 MHz) 1.70 (d, 3H), 3.78 (s, 3H), 5.51 (q, 1H), 5.76 (s, 2H), 6.95 (d, 1H), 7.16 (d, 1H), 7.28 (dd, 1H), 7.37 (d, 1H), 7.69 (m, 4H), 8.16 (s, 1H), 8.43 (s, 1H), 8.52 (s, 2H), 10.48 (s, 1H); Mass spectrum MH+ 455.

Aufarbeitung

  1. extractionThe solution was extracted with 2N aqueous hydrogen chloride
  2. extractionextracted with DCM
  3. washThe organic phase was washed with brine
  4. customdried
  5. customevaporated to an oil which
  6. customcrystallised on trituration with ether

Quellen und Nachweise

ORD-Eintrag
ord-ce1a070996de4a31b3d67eb01a9293bc
Quelldatensatz
uspto-grants-2010_10
Patentnummer
US07820683B2

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