[((R)-2-{4-[3-Chloro-4-(pyridin-2-ylmethoxy)phenylamino]quinazolin-5-yloxy}propylcarbamoyl)methyl]methylcarbamic acid tert-butyl ester → N1-{(2R)-2-[(4-{[3-Chloro-4-(pyridin-2-ylmethoxy)phenyl]amino}quinazolin-5-yl)oxy]propyl}-N2-methylglycinamide

HRID 1864351Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1864351
C(O[C:6](=O)[N:7]([CH2:9][C:10](=[O:42])[NH:11][CH2:12][C@H:13]([O:15][C:16]1[CH:25]=[CH:24][CH:23]=[C:22]2[C:17]=1[C:18]([NH:26][C:27]1[CH:32]=[CH:31][C:30]([O:33][CH2:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][N:36]=3)=[C:29]([Cl:41])[CH:28]=1)=[N:19][CH:20]=[N:21]2)[CH3:14])C)(C)(C)C>FC(F)(F)C(O)=O>[Cl:41][C:29]1[CH:28]=[C:27]([NH:26][C:18]2[C:17]3[C:22](=[CH:23][CH:24]=[CH:25][C:16]=3[O:15][C@H:13]([CH3:14])[CH2:12][NH:11][C:10](=[O:42])[CH2:9][NH:7][CH3:6])[N:21]=[CH:20][N:19]=2)[CH:32]=[CH:31][C:30]=1[O:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][N:36]=1

Komponenten

3

Edukt 1

HCID 57974348[((R)-2-{4-[3-Chloro-4-(pyridin-2-ylmethoxy)phenylamino]quinazolin-5-yloxy}propylcarbamoyl)methyl]methylcarbamic acid tert-butyl ester

Produkt 1

HCID 57974349N1-{(2R)-2-[(4-{[3-Chloro-4-(pyridin-2-ylmethoxy)phenyl]amino}quinazolin-5-yl)oxy]propyl}-N2-methylglycinamideAusbeute 15 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6422Trifluoroacetic acidLösungsmittel

Versuchsvorschrift

[((R)-2-{4-[3-Chloro-4-(pyridin-2-ylmethoxy)phenylamino]quinazolin-5-yloxy}propylcarbamoyl)methyl]methylcarbamic acid tert-butyl ester (obtained as described in Example 123, 0.50 g) was stirred in trifluoroacetic acid (5 ml) for 20 hours. Volatile material was removed by evaporation and the residue was purified by chromatography, eluting with aqueous ammonia (0.880), methanol, DCM (1:10:90). Evaporation of the appropriate fractions gave the title compound as a solid (60 mg, 15%); (DMSO-d6 @ 373k) 1.47-1.50 (d, 3H), 2.20 (s, 3H), 3.10 (s, 2H), 3.45-3.55 (q, 1H), 3.55-3.65 (q, 1H), 4.85-5.00 (m, 1H), 5.25 (s, 2H), 7.15-7.25 (q, 2H), 7.25-7.30 (m, 2H), 7.55-7.65 (t, 1H), 7.70-7.80 (m, 2H), 8.20 (s, 1H), 8.50 (s, 1H), 8.55-8.60 (d, 1H), 9.85-9.95 (bs, 1H); Mass spectrum MH+ 507.

Aufarbeitung

  1. customVolatile material was removed by evaporation
  2. customthe residue was purified by chromatography
  3. washeluting with aqueous ammonia (0.880), methanol, DCM (1:10:90)
  4. customEvaporation of the appropriate fractions

Quellen und Nachweise

ORD-Eintrag
ord-48431c9dad3642c5bd0d9e578c606cb2
Quelldatensatz
uspto-grants-2009_12
Patentnummer
US07625908B2

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