Ammonia → HCID 68676425, compound

HRID 1442982Notes

Reaction equation

HRID 1442982 reaction equation
FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:10]=[C:11]([CH:39]=[CH:40][C:41]=1[F:42])[NH:12][C:13]1[C:22]2[C:17](=[CH:18][C:19]([O:37][CH3:38])=[CH:20][C:21]=2[O:23][CH2:24][C@@H:25]2[CH2:29][CH2:28][CH2:27][N:26]2C(OC(C)(C)C)=O)[N:16]=[CH:15][N:14]=1.N>CO>[Cl:8][C:9]1[CH:10]=[C:11]([NH:12][C:13]2[C:22]3[C:17](=[CH:18][C:19]([O:37][CH3:38])=[CH:20][C:21]=3[O:23][CH2:24][C@@H:25]3[CH2:29][CH2:28][CH2:27][NH:26]3)[N:16]=[CH:15][N:14]=2)[CH:39]=[CH:40][C:41]=1[F:42]

Participants

5

Reactant 3

HCID 222AmmoniaHCID 6422Trifluoroacetic acidHCID 86607800HCID 86607800, compound

Product 1

HCID 68676425HCID 68676425, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Trifluoroacetic acid (25 ml) was added in one portion to tert-butyl (2S)-2-[({4-[3-chloro-4-fluoro-anilino]-7-methoxyquinazolin-5-yl}oxy)methyl]pyrrolidine-1-carboxylate (1.6 g) and the solution was stirred at room temperature for 1 hour 30 minutes. The solution was then concentrated in vacuo and azeotroped three times with ether to leave an orange oil. 7N Ammonia in methanol (5 ml) was added and the mixture was stirred for 10 minutes. The mixture was then concentrated in vacuo to leave an orange oil and purified by column chromatography using 0-10% methanol in DCM as eluent to give N-(3-chloro-4-fluorophenyl)-7-methoxy-5-[(2S)-pyrrolidin-2-ylmethoxy]-quinazolin-4-amine as a light yellow solid (1.15 g, 75% over two steps); Mass spectrum MH+ 403.

Workup

  1. concentrationThe solution was then concentrated in vacuo
  2. customazeotroped three times with ether
  3. customto leave an orange oil
  4. stirringthe mixture was stirred for 10 minutes
  5. concentrationThe mixture was then concentrated in vacuo
  6. customto leave an orange oil
  7. custompurified by column chromatography

Sources & evidence

ORD record
ord-25889389755441879c6142c9baf967c6
Source dataset
uspto-grants-2010_02
Patent number
US07659279B2

Reaction notes

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