Methylamine → HCID 67238793, compound

HRID 1027918Notes

Reaction equation

HRID 1027918 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].[CH3:39][N:40]1CCOCC1.CN>C1COCC1.C(Cl)Cl>[Cl:34][C:30]1[C:29]([F:35])=[C:28]([NH:27][C:18]2[C:17]3[C:22](=[CH:23][C:24]([O:25][CH3:26])=[C:15]([O:14][C@H:11]4[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[C@H:9]([C:36]([NH:40][CH3:39])=[O:38])[CH2:10]4)[CH:16]=3)[N:21]=[CH:20][N:19]=2)[CH:33]=[CH:32][CH:31]=1

Participants

6

Reactant 3

HCID 6329MethylamineHCID 79724-MethylmorpholineHCID 58318669HCID 58318669, compound

Product 1

HCID 67238793HCID 67238793, compoundYield 100.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent3×

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 (4 g, 7.31 mmol, prepared as described in Example 1) in THF (50 ml) was cooled to −15° C. (acetone/ice). NMM (1.21 ml, 11.0 mmol) was added to the solution followed by IBCF (1.24 ml, 9.51 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 a 2.0M solution of methylamine in THF (10 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)-4-({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}oxy)-2-[(methylamino)carbonyl]piperidine-1-carboxylate (4.1 g, 100%) as pale yellow foam which was used without further purification; Mass Spectrum: (M+H)+ 560.1.

Workup

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

Sources & evidence

ORD record
ord-8c26669b55bb47da8f6770e0cb756585
Source dataset
uspto-grants-2014_05
Patent number
US08735410B2

Reaction notes

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