Acetic Acid → N-[4-(benzyloxy)phenyl]-7-methoxy-6-[5-({[2-(methanesulphonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamine

HRID 1497631Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1497631
Cl.[CH2:2]([O:9][C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:34][CH3:35])=[C:24]([C:27]4[O:31][C:30]([CH:32]=O)=[CH:29][CH:28]=4)[CH:25]=3)[N:20]=[CH:19][N:18]=2)=[CH:12][CH:11]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH3:36][S:37]([CH2:40][CH2:41][NH2:42])(=[O:39])=[O:38].C(O)(=O)C.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH2:2]([O:9][C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:34][CH3:35])=[C:24]([C:27]4[O:31][C:30]([CH2:32][NH:42][CH2:41][CH2:40][S:37]([CH3:36])(=[O:39])=[O:38])=[CH:29][CH:28]=4)[CH:25]=3)[N:20]=[CH:19][N:18]=2)=[CH:12][CH:11]=1)[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

Komponenten

7

Edukt 5

HCID 176Acetic AcidHCID 8471TriethylamineHCID 43405612-(Methylsulfonyl)ethanamineHCID 5049666Sodium triacetoxyborohydrideHCID 219520305-(4-(4-Benzyloxy-phenylamino)-7-methoxy-quinazolin-6-yl)-furan-2-carbaldehyde hydrochloride

Produkt 1

HCID 9893981N-[4-(benzyloxy)phenyl]-7-methoxy-6-[5-({[2-(methanesulphonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamineAusbeute 48,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 111,2-DichloroethaneLösungsmittel

Versuchsvorschrift

Prepared in a similar manner to Procedure D from 5-(4-(4-benzyloxy-phenylamino)-7-methoxy-quinazolin-6-yl)-furan-2-carbaldehyde hydrochloride (78 mg, 0.16 mmol), 2-methanesulphonylethylamine (33 mg, 0.27 mmol), acetic acid (15 mg, 0.25 mmol) and triethylamine (18 mg, 0.18 mmol) in 3 ml of 1,2-dichloroethane added to sodium triacetoxyborohydride (102 mg, 0.48 mmol) portionwise over a two day period. The reaction mixture was stirred four days and then partitioned between 10 ml of 0.5M NaHCO3 solution and 50 ml of ethyl acetate. The organic solution was dried with Na2SO4 and concentrated in vacuo. The residue was chromatographed on silica gel with methanol/methylene chloride (1:49 to 2:48). The resulting solid was crystallized from a small volume of ethyl acetate, suspended in ether and filtered to give 43 mg of product as a pale yellow solid. δ1H NMR (400 MHz, DMSO-d6) 9.78 (s, 1H), 8.73 (s, 1H), 8.42 (s, 1H), 6.64 (d, 2H), 7.47 (m, 2H), 7.40 (m, 2H), 7.33 (m, 1H), 7.25 (s, 1H), 7.04 (d, 2H), 6.98 (d, 1H), 6.46 (d, 1H), 5.12 (s, 2H), 4.04 (s, 3H), 3.86 (s, 2H), 3.28 (t, 2H), 3.01 (s, 3H), 2.99 (t, 2H). ESI-MS m/z 559 (M+1).

Aufarbeitung

  1. custompartitioned between 10 ml of 0.5M NaHCO3 solution and 50 ml of ethyl acetate
  2. dry with materialThe organic solution was dried with Na2SO4
  3. concentrationconcentrated in vacuo
  4. customThe residue was chromatographed on silica gel with methanol/methylene chloride (1:49 to 2:48)
  5. customThe resulting solid was crystallized from a small volume of ethyl acetate
  6. filtrationfiltered

Quellen und Nachweise

ORD-Eintrag
ord-3078e374e77c404c8ff736a475ddb076
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09199973B2

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