Ammonia → HCID 58318668, compound

HRID 1027915Notes

Reaction equation

HRID 1027915 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([O:14][C:15]2[CH:16]=[C:17]3[C:22](=[CH:23][C:24]=2[O:25][CH3:26])[N:21]=[CH:20][N:19]=[C:18]3[NH:27][C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([Cl:34])[C:29]=2[F:35])[CH2:10][C@H:9]1[C:36]([OH:38])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C[N:40]1CCOCC1.N>C1COCC1.C(Cl)Cl>[NH2:40][C:36]([C@@H:9]1[CH2:10][C@@H:11]([O:14][C:15]2[CH:16]=[C:17]3[C:22](=[CH:23][C:24]=2[O:25][CH3:26])[N:21]=[CH:20][N:19]=[C:18]3[NH:27][C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([Cl:34])[C:29]=2[F:35])[CH2:12][CH2:13][N:8]1[C:6]([O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[O:7])=[O:38]

Participants

6

Reactant 3

HCID 222AmmoniaHCID 79724-MethylmorpholineHCID 58318669HCID 58318669, compound

Product 1

HCID 58318668HCID 58318668, compoundYield 100%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A stirred solution of (2S,4S)-1-(tert-butoxycarbonyl)-4-({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}oxy)piperidine-2-carboxylic acid (3) (5 g, 9.16 mmol) in THF (50 ml) was cooled to −15° C. (acetone/ice). NMM (1.5 ml, 13.7 mmol) was added to the solution followed by IBCF (1.54 ml, 11.9 mmol). The reaction mixture was held at −15° C. (the formation of the mixed anhydride was monitored by TLC (THF)). After 5-10 minutes, the reaction mixture was treated with concentrated aqueous ammonia (3 ml) at −15° C. and allowed to warm to room temperature. The reaction mixture was diluted with DCM (250 ml), washed with water (2×20 ml) and concentrated to give tert-butyl (2S,4S)-2-(aminocarbonyl)-4-({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}oxy)piperidine-1-carboxylate (4) (5 g, 100%) as a pale yellow foam which was used without further purification; Mass Spectrum: (M+H)+ 546.1.

Workup

  1. customwas held at −15° C.
  2. washwashed with water (2×20 ml)
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-5f9bc35de0e3489caa3ab491db615cc8
Source dataset
uspto-grants-2014_05
Patent number
US08735410B2

Reaction notes

Loading…