Sodium Bicarbonate → HCID 136344271, compound

HRID 1442993Notes

Reaction equation

HRID 1442993 reaction equation
C([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([NH:19][C:20]3[CH:25]=[CH:24][C:23]([F:26])=[C:22]([Cl:27])[CH:21]=3)=[N:14][CH:15]=[N:16]2)=[C:11]([O:28][CH2:29][C@H:30]2[CH2:34][CH2:33][CH2:32][N:31]2C(OC(C)(C)C)=O)[CH:10]=1)C1C=CC=CC=1.C(=O)([O-])O.[Na+]>FC(F)(F)C(O)=O>[Cl:27][C:22]1[CH:21]=[C:20]([CH:25]=[CH:24][C:23]=1[F:26])[NH:19][C:13]1[C:12]2[C:17](=[CH:18][C:9]([OH:8])=[CH:10][C:11]=2[O:28][CH2:29][C@H:30]2[CH2:34][CH2:33][CH2:32][NH:31]2)[N:16]=[CH:15][N:14]=1

Participants

4

Reactant 2

HCID 516892Sodium BicarbonateHCID 86607803tert-butyl (2R)-2-[({7-(benzyloxy)-4-[3-chloro-4-fluoroanilino]quinazolin-5-yl}oxy)methyl]pyrrolidine-1-carboxylate

Product 1

HCID 136344271HCID 136344271, compoundYield 20%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
70 °C

Procedure

tert-Butyl (2R)-2-[({7-(benzyloxy)-4-[3-chloro-4-fluoroanilino]quinazolin-5-yl}oxy)methyl]pyrrolidine-1-carboxylate (1.5 g) was taken up in trifluoroacetic acid (15 ml) and the solution was heated at 70° C. for 18 hours. The solution was cooled to room temperature and then concentrated in vacuo to leave a brown residue. Saturated aqueous sodium hydrogen carbonate was added to the residue and the aqueous mixture was extracted with ethyl acetate. The layers were separated and the organic layer was dried (MgSO4) and concentrated in vacuo to leave a brown oil. Purification by flash chromatography, using 5:1:84 methanol:7N ammonia in methanol:DCM→20:1:79 methanol:7N ammonia in methanol:DCM as eluent, followed by trituration with ether gave 4-[3-chloro-4-fluoro-anilino]-5-[(2R)-pyrrolidin-2-ylmethoxy]quinazolin-7-ol as an off-white solid (200 mg, 20%); NMR Spectrum (DMSO-d6) 10.40 (brs, 1H), 8.40 (s, 1H), 8.15 (m, 1H), 7.95 (m, 1H), 7.40 (m, 1H), 6.75 (m, 2H), 4.30 (m, 1H), 4.05 (m, 1H), 3.60-3.50 (m, 1H), 3.0-2.80 (m, 2H), 1.95-1.80 (m, 1H), 1.75-1.65 (m, 2H), 1.50-1.40 (m, 1H); Mass spectrum MH+ 391.

Workup

  1. temperatureThe solution was cooled to room temperature
  2. concentrationconcentrated in vacuo
  3. customto leave a brown residue
  4. extractionthe aqueous mixture was extracted with ethyl acetate
  5. customThe layers were separated
  6. dry with materialthe organic layer was dried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customto leave a brown oil
  9. customPurification by flash chromatography

Sources & evidence

ORD record
ord-77042358e09d46eda2a5015df3751ded
Source dataset
uspto-grants-2010_02
Patent number
US07659279B2

Reaction notes

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