Glycolic Acid → HCID 11751862, compound

HRID 1442997Notes

Reaction equation

HRID 1442997 reaction equation
[C:1]([OH:5])(=O)[CH2:2][OH:3].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[Cl:30][C:31]1[CH:32]=[C:33]([NH:38][C:39]2[C:48]3[C:43](=[CH:44][C:45]([O:56][CH2:57][CH3:58])=[CH:46][C:47]=3[O:49][CH2:50][C@H:51]3[CH2:55][CH2:54][CH2:53][NH:52]3)[N:42]=[CH:41][N:40]=2)[CH:34]=[CH:35][C:36]=1[F:37].C(N(CC)C(C)C)(C)C>C(Cl)Cl.CS(C)=O>[Cl:30][C:31]1[CH:32]=[C:33]([CH:34]=[CH:35][C:36]=1[F:37])[NH:38][C:39]1[C:48]2[C:43](=[CH:44][C:45]([O:56][CH2:57][CH3:58])=[CH:46][C:47]=2[O:49][CH2:50][C@H:51]2[CH2:55][CH2:54][CH2:53][N:52]2[C:1](=[O:5])[CH2:2][OH:3])[N:42]=[CH:41][N:40]=1

Participants

7

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 68675397HCID 68675397, compound

Product 1

HCID 11751862HCID 11751862, compoundYield 39%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent

Procedure

Glycolic acid (22 mg) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, 110 mg) were added sequentially, each in one portion, to a stirred solution of N-(3-chloro-4-fluorophenyl)-7-ethoxy-5-[(2R)-pyrrolidin-2-ylmethoxy]-quinazolin-4-amine (81 mg) and N,N-diisopropylethylamine (68 μl) in DCM (2.5 ml) at room temperature. The reaction mixture was stirred for 16 hours and then concentrated in vacuo to leave a brown residue. The residue was taken up in a 7:2:1 mixture of DMSO:acetonitrile:water, filtered and then purified by reverse phase HPLC. The fractions containing the required product were combined, basified by the addition of potassium carbonate and then extracted with DCM. The organic layer was dried (MgSO4) and then concentrated in vacuo to give the title compound as a white solid (36 mg, 39%); NMR Spectrum (DMSO-d6 at 373 K) 9.80 (br s, 1H), 8.40 (s, 1H), 8.15 (m, 1H), 7.65 (m, 1H), 7.33 (m, 1H), 6.80 (m, 2H), 4.60 (m, 1H), 4.50 (m, 1H), 4.30-4.10 (m, 4H), 4.0 (m, 2H), 3.50-3.40 (m, 2H), 2.10-1.85 (m, 4H), 1.40 (t, 3H); Mass spectrum MH+ 475.

Workup

  1. customat room temperature
  2. concentrationconcentrated in vacuo
  3. customto leave a brown residue
  4. filtrationacetonitrile:water, filtered
  5. custompurified by reverse phase HPLC
  6. additionThe fractions containing the required product
  7. additionbasified by the addition of potassium carbonate
  8. extractionextracted with DCM
  9. dry with materialThe organic layer was dried (MgSO4)
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3be382ea6a0044f4b8f7a67d8eb86686
Source dataset
uspto-grants-2010_02
Patent number
US07659279B2

Reaction notes

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