4-Methylmorpholine → HCID 54162264, compound

HRID 1433022Notes

Reaction equation

HRID 1433022 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]([C:20](=[O:29])[CH2:21][O:22][C:23]4[S:24][C:25]([Cl:28])=[CH:26][CH:27]=4)[CH2:15][CH:14]3[C:30]([OH:32])=O)=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1.[CH3:33][N:34]1CCOCC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN.Cl>CN(C=O)C>[CH3:33][NH:34][C:30]([CH:14]1[CH2:15][N:16]([C:20](=[O:29])[CH2:21][O:22][C:23]2[S:24][C:25]([Cl:28])=[CH:26][CH:27]=2)[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:32]

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 53638350HCID 53638350, compound

Product 1

HCID 54162264HCID 54162264, compoundYield 71.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Water (1 mL) is added to a solution containing (±)-1-(4-amino-quinazolin-7-ylmethyl)-4-[(5-chloro-thiophen-2-yloxy)-acetyl]-6-oxo-piperazine-2-carboxylic acid methyl ester (20 mg, 0.03 mmol), EXAMPLE 808, in a 1:1 mixture of THF/MeOH (2 mL). At ambient temperature, LiOH monohydrate (3 mg, 0.07 mmol) is then added. After 16 h, the reaction mixture is diluted with 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 25 mg (>100%) of the associated acid as a white solid after lyophilization which is used directly in the next reaction. To a mixture containing (+/−)-1-(4-amino-quinazolin-7-ylmethyl)-4-[(5-chloro-thiophen-2-yloxy)-acetyl]-6-oxo-piperazine-2-carboxylic acid (12 mg, 0.02 mmol), N-methylmorpholine (19 mg, 0.19 mmol), and HATU (22 mg, 0.05 mmol) in anhydrous DMF (1 mL) is added MeNH2 hydrochloride (5 mg, 0.19 mmol). The reaction mixture is stirred 1 h at ambient temperature and then concentrated to dryness. The residue is dissolved in 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 7 mg (58%) of the title compound as a white solid.

Workup

  1. customis used directly in the next reaction
  2. concentrationconcentrated to dryness
  3. dissolutionThe residue is dissolved in water
  4. custompurified by reverse-phase HPLC [Buffer A: water

Sources & evidence

ORD record
ord-ebac6379f1d34c90bd3068af33184a14
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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