Diisopropylethylamine → N-[4-(Benzyloxy)phenyl]-7-fluoro-6-[5-({[2-(methanesulphonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamine

HRID 1893979Notes

Reaction equation

HRID 1893979 reaction equation
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]([F:34])=[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.C(N(C(C)C)CC)(C)C.[CH3:44][S:45]([CH2:48][CH2:49][NH2:50])(=[O:47])=[O:46].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.C(O)(=O)C>[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]([F:34])=[C:24]([C:27]4[O:31][C:30]([CH2:32][NH:50][CH2:49][CH2:48][S:45]([CH3:44])(=[O:47])=[O:46])=[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

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 43405612-(Methylsulfonyl)ethanamineHCID 5049666Sodium triacetoxyborohydrideHCID 219520395-(4-(4-Benzyloxy-phenylamino)-7-fluoro-quinazolin-6-yl)-furan-2-carbaldehyde hydrochloride

Product 1

HCID 9872163N-[4-(Benzyloxy)phenyl]-7-fluoro-6-[5-({[2-(methanesulphonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamineYield 61%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 176Acetic AcidSolvent

Procedure

Prepared according to Procedure D from a mixture of 5-(4-(4-benzyloxy-phenylamino)-7-fluoro-quinazolin-6-yl)-furan-2-carbaldehyde hydrochloride (0.13 grams) in 1,2-dichloroethane (3 ml), diisopropylethylamine (65 mg), acetic acid (45 mg), 2-methanesulphonylethylamine (0.125 grams), and sodium triacetoxyborohydride (0.27 grams). The mixture was stirred for 18 hours. The reaction mixture was quenched with methanol (3 ml) and poured into a separatory funnel containing aqueous saturated sodium hydrogen carbonate (100 ml) and ethyl acetate (100 ml). The mixture was extracted. The organic layer was washed with water. The organic layer was dried over magnesium sulfate, filtered, and concentrated. The residue was treated with ethyl acetate/hexanes and collected by filtration (0.083 g, 61% yield). δ1H NMR (400 MHz, DMSO-d6) 9.98 (s, 1H), 8.83 (d, 1H), 8.44 (s, 1H), 7.58 (m, 3H), 7.44 (m, 2H), 7.37 (m, 2H), 7.31 (m, 1H), 7.03 (d, 1H), 6.91 (m, 1H), 6.5 (d, 1H), 5.1 (s, 2H), 3.84 (s, 1H), 3.25 (m, 2H), 2.99 (s, 3H), 2.96 (m, 2H). ESI-MS m/z 545 (M−1).

Workup

  1. customPrepared
  2. customThe reaction mixture was quenched with methanol (3 ml)
  3. additionpoured into a separatory funnel
  4. additioncontaining aqueous saturated sodium hydrogen carbonate (100 ml) and ethyl acetate (100 ml)
  5. extractionThe mixture was extracted
  6. washThe organic layer was washed with water
  7. dry with materialThe organic layer was dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. additionThe residue was treated with ethyl acetate/hexanes
  11. filtrationcollected by filtration (0.083 g, 61% yield)

Sources & evidence

ORD record
ord-0ee492ccb2034945b4e5e4f0521e0afc
Source dataset
uspto-grants-2013_08
Patent number
US08513262B2

Reaction notes

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