Diisopropylethylamine → HCID 58267794, compound

HRID 631368Notes

Reaction equation

HRID 631368 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][C:27]([O:33][C@H:34]5[CH2:38][CH2:37][NH:36][CH2:35]5)=[C:28]([O:31][CH3:32])[CH:29]=4)[N:24]=[CH:23][N:22]=3)[CH:15]=2)=[O:12])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C(N(CC)C(C)C)(C)C.FC(F)(F)S(O[CH2:54][CH:55]([F:57])[F:56])(=O)=O>C(Cl)Cl>[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][C:27]([O:33][C@H:34]5[CH2:38][CH2:37][N:36]([CH2:54][CH:55]([F:57])[F:56])[CH2:35]5)=[C:28]([O:31][CH3:32])[CH:29]=4)[N:24]=[CH:23][N:22]=3)[CH:15]=2)=[O:12])[CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 27740892,2-Difluoroethyl trifluoromethanesulfonateHCID 58267880(S)-1-(5-tert-butylisoxazol-3-yl)-3-{3-[6-methoxy-7-(pyrrolidin-3-yloxy)quinazolin-4-yloxy]phenyl}urea

Product 1

HCID 58267794HCID 58267794, compoundYield 44.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of (5)-1-(5-tert-butylisoxazol-3-yl)-3-{3-[6-methoxy-7-(pyrrolidin-3-yloxy)quinazolin-4-yloxy]phenyl}urea (0.198 g, 0.38 mmol) and N,N-diisopropylethylamine (0.5 mL) in CH2Cl2 (10 mL) was added 2,2-difluoroethyl trifluoromethanesulfonate (0.128 g. 0.6 mmol) and it was stirred at 40° C. for 1 hour. It was quenched with saturated NaHCO3 and extracted with CH2Cl2. Extracts were dried over MgSO4 and concentrated under reduced pressure. It was purified by silica gel chromatography with 70-85% EtOAc/hexane as eluants to afford (S)-1-(5-tert-Butylisoxazol-3-yl)-3-(3-{7-[1-(2,2-difluoroethyl)pyrrolidin-3-yloxy]-6-methoxyquinazolin-4-yloxy}phenyl)urea as solid (0.098 g, 44%). 1H NMR (300 MHz, CDCl3) δ 9.4 (s, 1H), 8.62 (s, 1H), 7.81 (s, 1H), 7.65 (t, 1H), 7.54 (s, 1H), 7.40 (t, 1H), 7.33 (m, 1H), 7.19 (s, 1H), 7.00 (d, 1H), 5.93 (tt, 1H), 5.87 (s, 1H), 5.05 (m, 1H), 4.03 (s, 3H), 3.20 (m, 1H), 3.89-3.09 (m, 4H), 2.8 (m, 1H), 2.5 (m, 1H), 2.15 (m, 1H), 1.33 (s, 9H); LC-MS (ESI) m/z 583 (M+H)+.

Workup

  1. customIt was quenched with saturated NaHCO3
  2. extractionextracted with CH2Cl2
  3. dry with materialExtracts were dried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customIt was purified by silica gel chromatography with 70-85% EtOAc/hexane as eluants

Sources & evidence

ORD record
ord-e2b44ddd8a404cb1933b28c1356a293f
Source dataset
uspto-grants-2016_04
Patent number
US09320739B2

Reaction notes

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