Glycolic Acid → HCID 11294151, compound

HRID 1442978Notes

Reaction equation

HRID 1442978 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][CH3:57])=[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>[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][CH3:57])=[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

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 68676425HCID 68676425, compound

Product 1

HCID 11294151HCID 11294151, compoundYield 50.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Glycolic acid (20 mg) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, 109 mg) were added sequentially, each in one portion, to a stirred solution of N-(3-chloro-4-fluorophenyl)-7-methoxy-5-[(2S)-pyrrolidin-2-ylmethoxy]-quinazolin-4-amine (96 mg) and N,N-diisopropylethylamine (83 μl) in DCM (3 ml) at room temperature under a nitrogen atmosphere. The reaction mixture was stirred for 16 hours 30 minutes and then diluted with DCM (10 ml) and washed with saturated aqueous sodium hydrogen carbonate and water. The organic layer was dried (MgSO4) and concentrated in vacuo to leave a yellow oil, which was purified by column chromatography using 0-10% methanol in dichloromethane as eluent to give the title compound as a white solid (55 mg, 50%); NMR Spectrum (DMSO-d6) 9.90 (s, 1H), 8.42 (s, 1H), 8.15 (dd, 1H), 7.70-7.60 (m, 1H), 7.40 (t, 1H), 6.88 (d, 1H), 6.78 (d, 1H), 4.65-4.53 (m, 2H), 4.40 (dd, 1H), 4.17 (dd, 1H), 4.03 (d, 1H), 3.90 (s, 3H), 3.45-3.35 (m, 3H), 2.10-1.82 (m, 4H); Mass spectrum MH+ 461.

Workup

  1. customat room temperature
  2. washwashed with saturated aqueous sodium hydrogen carbonate and water
  3. dry with materialThe organic layer was dried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customto leave a yellow oil, which
  6. customwas purified by column chromatography

Sources & evidence

ORD record
ord-c9223b14b8164a2cbf9ebfee8ce75cbc
Source dataset
uspto-grants-2010_02
Patent number
US07659279B2

Reaction notes

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