4-Methylmorpholine → (+/-)-1-(4-Amino-quinazolin-7-ylmethyl)-4-(5-chloro-1H-indol-2-ylmethyl)-6-oxo-piperazine-2-carboxylic acid methylamide

HRID 1433016Notes

Reaction equation

HRID 1433016 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([CH2:12][N:13]3[C:18](=[O:19])[CH2:17][N:16]([CH2:20][C:21]4[NH:22][C:23]5[C:28]([CH:29]=4)=[CH:27][C:26]([Cl:30])=[CH:25][CH:24]=5)[CH2:15][CH:14]3[C:31]([OH:33])=O)=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1.[CH3:34][N:35]1CCOCC1.Cl.CN.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH3:34][NH:35][C:31]([CH:14]1[CH2:15][N:16]([CH2:20][C:21]2[NH:22][C:23]3[C:28]([CH:29]=2)=[CH:27][C:26]([Cl:30])=[CH:25][CH:24]=3)[CH2:17][C:18](=[O:19])[N:13]1[CH2:12][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([NH2:1])=[N:3][CH:4]=[N:5]2)=[CH:10][CH:9]=1)=[O:33]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 6364545Methylamine hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 54503880(+/-)-1-(4-Amino-quinazolin-7-ylmethyl)-4-(5-chloro-1H-indol-2-ylmethyl)-6-oxo-piperazine-2-carboxylic acid

Product 1

HCID 57189062(+/-)-1-(4-Amino-quinazolin-7-ylmethyl)-4-(5-chloro-1H-indol-2-ylmethyl)-6-oxo-piperazine-2-carboxylic acid methylamideYield 153.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution containing (±)-1-(4-amino-quinazolin-7-ylmethyl)-4-(5-chloro-1H-indol-2-ylmethyl)-6-oxo-piperazine-2-carboxylic acid (25 mg, 0.03 mmol), EXAMPLE 785, and N-methylmorpholine (36 mg, 0.36 mmol) in anhydrous DMF (1 mL) is added methylamine hydrochloride (10 mg, 0.14 mmol) followed by HATU (40 mg, 0.10 mmol) at ambient temperature. After 3 h, the solvent is removed under high vacuum and the residue is dissolved in CH3CN/water and purified by reverse-phase HPLC [Buffer A: water w/0.1% TFA; Buffer B: CH3CN w/0.1% TFA; Gradient: 0% B to 60% B over 30 min] to provide 22 mg (88%) of the title compound as a white solid.

Workup

  1. customthe solvent is removed under high vacuum
  2. dissolutionthe residue is dissolved in CH3CN/water
  3. custompurified by reverse-phase HPLC [Buffer A: water

Sources & evidence

ORD record
ord-afa320140c294a9e85902193e3b04a46
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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