Ammonia → HCID 58318672, compound

HRID 1027926Notes

Reaction equation

HRID 1027926 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 58318649HCID 58318649, compound

Product 1

HCID 58318672HCID 58318672, compoundYield 102.6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

A stirred solution of (2R,4R)-1-(tert-butoxycarbonyl)-4-({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}oxy)piperidine-2-carboxylic acid (7) (0.13 g, 0.232 mmol) in THF (5 ml) was cooled to −15° C. (acetone/ice). NMM (0.035 g, 0.348 mmol) was added to the solution followed by IBCF (0.041 g, 0.301 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 aqueous ammonia in THF (0.2 ml) at −15° C. and allowed to warm to room temperature. The reaction mixture was diluted with DCM (20 ml), washed with water (2×2 ml) and concentrated to give tert-butyl (2R,4R)-2-(aminocarbonyl)-4-({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}oxy)piperidine-1-carboxylate (8) (0.13 g, 100%) as a pale yellow foam which was used without further purification; Mass Spectrum: (M+H)+ 544.0.

Workup

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

Sources & evidence

ORD record
ord-774211f803ab48a29941ee575c1e3850
Source dataset
uspto-grants-2014_05
Patent number
US08735410B2

Reaction notes

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