Sulfuric acid magnesium salt (1:1) → HCID 58267925, compound

HRID 871389Notes

Reaction equation

HRID 871389 reaction equation
[C:1]([C:5]1[O:9][N:8]=[C:7]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:20][C:21]3[C:30]4[C:25](=[CH:26][CH:27]=[C:28]([C:31]5[O:32][C:33]([CH:36]=O)=[CH:34][CH:35]=5)[CH:29]=4)[N:24]=[CH:23][N:22]=3)[CH:15]=2)=[O:12])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:38][S:39]([CH2:42][CH2:43][NH2:44])(=[O:41])=[O:40].[O-]S([O-])(=O)=O.[Mg+2].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl.C(O)(=O)C.CO>[C:1]([C:5]1[O:9][N:8]=[C:7]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:20][C:21]3[C:30]4[C:25](=[CH:26][CH:27]=[C:28]([C:31]5[O:32][C:33]([CH2:36][NH:44][CH2:43][CH2:42][S:39]([CH3:38])(=[O:41])=[O:40])=[CH:34][CH:35]=5)[CH:29]=4)[N:24]=[CH:23][N:22]=3)[CH:15]=2)=[O:12])[CH:6]=1)([CH3:3])([CH3:2])[CH3:4]

Participants

8

Reactant 4

HCID 24083Sulfuric acid magnesium salt (1:1)HCID 43405612-(Methylsulfonyl)ethanamineHCID 5049666Sodium triacetoxyborohydride2×HCID 86653509HCID 86653509, compound

Product 1

HCID 58267925HCID 58267925, compoundYield 25.3%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a mixture of 1-(5-tert-butylisoxazol-3-yl)-3-{3-[6-(5-formylfuran-2-yl)quinazolin-4-yloxy]phenyl}urea (0.17 g. 0.34 mmol), 2-(methylsulfonyl)ethanamine (0.15 g. 1.2 mmol), and MgSO4 in CH2Cl2 was added acetic acid (4 drops), followed by MeOH (1 mL). After the mixture was stirred at room temperature for 1 hour, NaBH(OAc)3 (0.212 g, 1 mmol) was added. After stirring the mixture at room temperature for more 2 hours, more NaBH(OAc)3 (0.212 g, 1 mmol) was added and stirred at room temperature overnight. The reaction was quenched with water, basified with saturated NaHCO3, and extracted with CH2Cl2. The extracts were dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by silica gel chromatography with 2-6% MeOH/EtOAc as eluants to afford 1-(5-tert-butylisoxazol-3-yl)-3-{3-[6-(5-{[2-(methylsulfonyl)ethylamino]methyl}furan-2-yl)quinazolin-4-yloxy]phenyl}urea as solid (0.052 g, 25%). 1H NMR (300 MHz, DMSO-d6) δ 9.59 (s, 1H), 9.02 (s, 1H), 8.70 (s, 1H), 8.52 (s, 1H), 8.38 (d, 1H), 8.03 (d, 1H), 7.61 (s, 1H), 7.43 (t, 1H), 7.31 (d, 1H), 7.23 (d, 1H), 7.03 (d, 1H), 6.48 (m, 2H), 3.83 (br, 2H), 3.24 (t, 2H), 3.02 (s, 3H), 2.97 (br, 2H), 1.27 (s, 9H); LC-MS (ESI) m/z 605 (M+H)+.

Workup

  1. stirringAfter stirring the mixture at room temperature for more 2 hours
  2. stirringstirred at room temperature overnight
  3. customThe reaction was quenched with water
  4. extractionextracted with CH2Cl2
  5. dry with materialThe extracts were dried over MgSO4
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by silica gel chromatography with 2-6% MeOH/EtOAc as eluants

Sources & evidence

ORD record
ord-b5cc6adb4f31445c8dc7a196852b5483
Source dataset
uspto-grants-2015_03
Patent number
US08969587B2

Reaction notes

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