Acetic Acid → N-(3-Trifluoromethyl-4-benzyloxyphenyl)-6-[5-({[2-(methanesulphonyl)ethyl]amino}methyl)-4-furyl]-4-quinazolinamine

HRID 1403793Notes

Reaction equation

HRID 1403793 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:26]4OC(C=O)=[CH:28][CH:27]=4)[CH:24]=3)[N:19]=[CH:18][N:17]=2)=[CH:11][C:10]=1[C:33]([F:36])([F:35])[F:34])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:37][S:38]([CH2:41][CH2:42][NH2:43])(=[O:40])=[O:39].[C:44]([OH:47])(=O)[CH3:45].C([BH3-])#N.[Na+]>ClCCl.C(OCC)(=O)C>[F:36][C:33]([F:34])([F:35])[C:10]1[CH:11]=[C:12]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:26]4[CH:27]=[CH:28][O:47][C:44]=4[CH2:45][NH:43][CH2:42][CH2:41][S:38]([CH3:37])(=[O:40])=[O:39])[CH:24]=3)[N:19]=[CH:18][N:17]=2)[CH:13]=[CH:14][C:9]=1[O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 43405612-(Methylsulfonyl)ethanamineHCID 5003444Sodium cyanoborohydrideHCID 219520795-(4-(4-Benzyloxy-3-trifluoromethylphenylamino)-quinazolin-6-yl)-furan-2-carbaldehyde

Product 1

HCID 21952104N-(3-Trifluoromethyl-4-benzyloxyphenyl)-6-[5-({[2-(methanesulphonyl)ethyl]amino}methyl)-4-furyl]-4-quinazolinamineYield 43%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

The mixture of 5-(4-(4-benzyloxy-3-trifluoromethylphenylamino)-quinazolin-6-yl)-furan-2-carbaldehyde (211 mg, 0.40 mmol), 2-methanesulphonyl-ethylamine (99 mg, 2.0 mmol), acetic acid (0.5 ml) in dichloromethane (15 ml) was stirred at room temperature for 1.5 hours then was heated to reflux for 1 hour. The mixture was cooled to 0° C. with ice bath. Sodium cyanoborohydride (50 mg, 0.8 mmol) was added at 0° C. The reaction mixture then was stirred at room temperature for 1 hour. Diluted with ethyl acetate (50 ml), then quenched with saturated sodium bicarbonate solution slowly. Extracted with ethyl acetate and the combined organic extracts were washed with brine, dried over MgSO4 and concentrated in vacuo. Purification of the resulting residue was accomplished using flash chromatography on silica gel with 2% methanol in ethyl acetate which afforded a yellow solid (0.10 g, 43% yield). H1 NMR (400 MHz, DMSO). δ 10.0 (s, 1H), 8.7 (s, 1H), 8.5 (s, 1H), 8.1 (d, 1H), 8.1 (s, 2H), 7.8 (d, 1H), 7.4 (m, 5H), 7.3 (m, 1H), 7.0 (d, 1H), 6.5 (d, 1H), 5.3 (s, 2H), 3.8 (s, 2H), 3.2 (m, 2H), 3.0 (s, 3H), 2.9 (m, 2H). ESI-MS m/z 597 (M+H)+.

Workup

  1. temperaturethen was heated
  2. temperatureto reflux for 1 hour
  3. temperatureThe mixture was cooled to 0° C. with ice bath
  4. stirringThe reaction mixture then was stirred at room temperature for 1 hour
  5. customquenched with saturated sodium bicarbonate solution slowly
  6. extractionExtracted with ethyl acetate
  7. washthe combined organic extracts were washed with brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated in vacuo
  10. customPurification of the resulting residue

Sources & evidence

ORD record
ord-11fec7a07e834a39838afdf971576a97
Source dataset
uspto-grants-2014_12
Patent number
US08912205B2

Reaction notes

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