Water → HCID 67297973, compound

HRID 1520354Notes

Reaction equation

HRID 1520354 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[C:4]([C:14]2[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=2)[N:3]=1.[F:20][C:21]1[CH:22]=[C:23]2[C:27](=[CH:28][CH:29]=1)[NH:26][C:25](=[O:30])[C:24]12[O:34][CH2:33][CH2:32][O:31]1.[OH-:35].[K+].O>CS(C)=O>[F:20][C:21]1[CH:29]=[CH:28][C:27]([NH:26][C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[CH:10]=3)[N:5]=[C:4]([C:14]3[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=3)[N:3]=2)=[C:23]([C:24]2([C:25]([OH:35])=[O:30])[O:34][CH2:33][CH2:32][O:31]2)[CH:22]=1

Participants

6

Reactant 4

HCID 962WaterHCID 14797Potassium HydroxideHCID 2856422HCID 2856422, compoundHCID 86677067HCID 86677067, compound

Product 1

HCID 67297973HCID 67297973, compoundYield 32%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a mixture of 4-chloro-6-methoxy-2-(pyridin-3-yl)quinazoline (0.50 g, 1.84 mmol) and 5′-fluorospiro[[1,3]-dioxolane-2,3′-indolin]-2′-one (0.42 g, 2.02 mmol) in dry DMSO (4 mL) was added KOH powder (0.11 g, 2.02 mmol). The reaction mixture was stirred for 15 h at room temperature and then the reaction mixture was poured into water. The aqueous layer was washed with ethyl acetate 20 mL) and the resulting aqueous layer was acidified with 5N HCl to give a precipitate. The solid was filtered to give 2-(5-fluoro-2-(6-methoxy-2-(pyridin-3-yl)quinazolin-4-ylamino)phenyl)-1,3-dioxolane-2-carboxylic acid as a light yellow powder (0.27 g, 0.58 mmol, 32%). LCMS m/z=432 (M+1) (Method C) 1H NMR (300 MHz, DMSO) δ 9.50-9.38 (m, 2H), 8.69-8.59 (m, 2H), 8.42 (dd, J=9.7, 5.3 Hz, 1H), 7.86 (d, J=9.1 Hz, 1H), 7.64 (d, J=2.6 Hz, 1H), 7.61-7.41 (m, 4H), 4.25-4.11 (m, 4H), 3.98 (s, 3H).

Workup

  1. washThe aqueous layer was washed with ethyl acetate 20 mL) and the resulting aqueous layer
  2. customto give a precipitate
  3. filtrationThe solid was filtered

Sources & evidence

ORD record
ord-17044d37b436401d87fff9ea65d193ca
Source dataset
uspto-grants-2015_07
Patent number
US09073890B2

Reaction notes

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