Glycolic Acid → HCID 11213353, compound

HRID 857945Notes

Reaction equation

HRID 857945 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.Cl.[Cl:27][C:28]1[C:29]([F:54])=[C:30]([CH:51]=[CH:52][CH:53]=1)[NH:31][C:32]1[C:41]2[C:36](=[CH:37][C:38]([O:49][CH3:50])=[C:39]([O:42][CH:43]3[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]3)[CH:40]=2)[N:35]=[CH:34][N:33]=1.[C:55](O)(=[O:58])[CH2:56][OH:57].C(N(C(C)C)CC)(C)C>C(Cl)Cl>[Cl:27][C:28]1[C:29]([F:54])=[C:30]([CH:51]=[CH:52][CH:53]=1)[NH:31][C:32]1[C:41]2[C:36](=[CH:37][C:38]([O:49][CH3:50])=[C:39]([O:42][CH:43]3[CH2:48][CH2:47][N:46]([C:56](=[O:57])[CH2:55][OH:58])[CH2:45][CH2:44]3)[CH:40]=2)[N:35]=[CH:34][N:33]=1

Participants

6

Reactant 4

HCID 757Glycolic AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 574768654-(3-Chloro-2-fluoroanilino)-7-methoxy-6-(piperidin-4-yloxy)quinazoline dihydrochloride

Product 1

HCID 11213353HCID 11213353, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

HATU (28.9 g) was added to a stirred solution of 4-(3-chloro-2-fluoroanilino)-7-methoxy-6-(piperidin-4-yloxy)quinazoline dihydrochloride (30 g), glycolic acid (5.40 g) and di-isopropylethylamine (44.70 ml) in methylene chloride (900 ml). After 1.5 hours the reaction mixture was washed with sodium hydroxide solution (2M), water and saturated brine. The resulting product was then purified by flash chromatography on silica eluting with 3% MeOH/methylene chloride. The fractions containing the desired product were combined and reduced in vacuo to give the title product as a white solid which was recrystallised from acetonitrile (29.6 g); NMR Spectrum: (DMSO d6) 1.65–1.81 (m, 2H), 1.99–2.10 (m, 2H), 3.26–3.34 (m, 1H), 3.37–3.47 (m, 1H), 3.60–3.68 (m, 1H), 3.81–3.89 (m, 1H), 3.95 (s, 3H), 4.14 (d, 2H), 4.50 (t, 1H), 4.78 (m, 1H), 7.25 (s, 1H), 7.30 (t, 1H), 7.46–7.55 (m, 2H), 7.88 (s, 1H), 8.40 (s, 1H), 9.55 (s, 1H); Mass Spectrum: (M+H)+ 460.94.

Workup

  1. washAfter 1.5 hours the reaction mixture was washed with sodium hydroxide solution (2M), water and saturated brine
  2. customThe resulting product was then purified by flash chromatography on silica eluting with 3% MeOH/methylene chloride
  3. additionThe fractions containing the desired product

Sources & evidence

ORD record
ord-9b0e2213c5394c3aa6b35b0e8fe49dc1
Source dataset
uspto-grants-2006_12
Patent number
US07148230B2

Reaction notes

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