Glycolic Acid → HCID 11397395, compound

HRID 1443000Notes

Reaction equation

HRID 1443000 reaction equation
F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[Cl:25][C:26]1[CH:27]=[C:28]([CH:50]=[CH:51][C:52]=1[F:53])[NH:29][C:30]1[C:39]2[C:34](=[CH:35][C:36]([O:48][CH3:49])=[CH:37][C:38]=2[O:40][CH2:41][C@@H:42]2[NH:46][CH2:45][C@@H:44]([OH:47])[CH2:43]2)[N:33]=[CH:32][N:31]=1.C(N(CC)C(C)C)(C)C.[C:63](O)(=[O:66])[CH2:64][OH:65]>C(Cl)Cl.C(=O)([O-])O.[Na+]>[Cl:25][C:26]1[CH:27]=[C:28]([CH:50]=[CH:51][C:52]=1[F:53])[NH:29][C:30]1[C:39]2[C:34](=[CH:35][C:36]([O:48][CH3:49])=[CH:37][C:38]=2[O:40][CH2:41][C@@H:42]2[N:46]([C:64](=[O:65])[CH2:63][OH:66])[CH2:45][C@@H:44]([OH:47])[CH2:43]2)[N:33]=[CH:32][N:31]=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 68676927HCID 68676927, compound

Product 1

HCID 11397395HCID 11397395, compoundYield 80%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 516892Sodium BicarbonateSolvent

Procedure

O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, 171 mg) was added in one portion to a stirred solution of (3S,5R)-5-[({4-[3-chloro-4-fluoroanilino]-7-methoxyquinazolin-5-yl}oxy)methyl]pyrrolidin-3-ol (157 mg), N,N-diisopropylethylamine (131 μl) and glycolic acid (31 μl) in DCM (5 ml), under an atmosphere of nitrogen. The reaction mixture was stirred at room temperature for 4 hours and then diluted with DCM and saturated aqueous sodium hydrogen carbonate was added. The organic layer was separated, dried (Na2SO4) and then concentrated in vacuo to leave the crude product as a yellow waxy solid. Purification by column chromatography, using 0 to 10% methanol in DCM as eluent, gave the title compound as a white solid (144 mg, 80%); NMR spectrum (DMSO-d6) 10.17 (s, 1H), 8.53 (s, 1H), 8.14 (dd, 1H), 7.74-7.69 (m, 1H), 7.47 (t, 1H), 6.92 (d, 1H), 6.83 (d, 1H), 5.14-5.10 (m, 1H), 4.71-4.67 (m, 1H), 4.50-4.44 (m, 1H), 4.40-4.38 (m, 1H), 4.28-4.23 (m, 1H), 4.06-4.03 (m, 2H), 3.95 (s, 3H), 3.53-3.48 (m, 2H), 2.05-2.02 (m, 2H); Mass spectrum MH+ 477.

Workup

  1. additionwas added
  2. customThe organic layer was separated
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customto leave the crude product as a yellow waxy solid
  6. customPurification by column chromatography

Sources & evidence

ORD record
ord-6856784298d94e94b2ab671a0f13060a
Source dataset
uspto-grants-2010_02
Patent number
US07659279B2

Reaction notes

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