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

HRID 51146

反応式

HRID 51146 の反応式
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

参加物

7

反応物 5

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

生成物 1

HCID 9893981N-[4-(benzyloxy)phenyl]-7-methoxy-6-[5-({[2-(methanesulphonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamine収率 48.1%

試薬・触媒・溶媒 1

HCID 111,2-Dichloroethane溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-44394595eee7422b97a398ef31ae2e9d
出典データセット
uspto-grants-2004_03
特許番号
US06713485B2

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