4-Methylmorpholine → HCID 11569621, compound

HRID 600676Notes

Reaction equation

HRID 600676 reaction equation
[CH3:1][N:2]([CH3:23])[C:3](=[O:22])[NH:4][C:5]1[CH:10]=[C:9]([CH2:11][NH:12][C:13]2[CH:21]=[CH:20][CH:19]=[CH:18][C:14]=2[C:15]([OH:17])=O)[CH:8]=[CH:7][N:6]=1.[CH3:24][O:25][C:26]([C:28]1[N:29]([CH3:38])[N:30]=[C:31]2[C:36]=1[CH:35]=[CH:34][C:33]([NH2:37])=[CH:32]2)=[O:27].CN1CCOCC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH3:24][O:25][C:26]([C:28]1[N:29]([CH3:38])[N:30]=[C:31]2[C:36]=1[CH:35]=[CH:34][C:33]([NH:37][C:15](=[O:17])[C:14]1[CH:18]=[CH:19][CH:20]=[CH:21][C:13]=1[NH:12][CH2:11][C:9]1[CH:8]=[CH:7][N:6]=[C:5]([NH:4][C:3]([N:2]([CH3:1])[CH3:23])=[O:22])[CH:10]=1)=[CH:32]2)=[O:27]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 23118985HCID 23118985, compoundHCID 45496744HCID 45496744, compound

Product 1

HCID 11569621HCID 11569621, compoundYield 35.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-{[2-(3,3-Dimethyl-ureido)-pyridin-4-ylmethyl]-amino}-benzoic acid (112 mg, 0.35 mmol), 6-amino-2-methyl-2H-indazole-3-carboxylic acid methyl ester (62 mg, 0.3 mmol), N-methylmorpholine (0.09 mL, 0.82 mmol) and HATU (152 mg, 0.4 mmol) were suspended in dry DMF (3 mL) and stirred at rt overnight. The reaction mixture was concentrated in vacuo and the residue partitioned between dichloromethane. The organic phase was washed consecutively with saturated aqueous sodium hydrogencarbonate solution, water and brine, dried and concentrated in vacuo. The residue was purified by chromatography on Isolute® flash silica gel (Separtis) (Gradient elution: 100% CH2Cl2 to CH2Cl2/EtOH 9:1) to give 6-(2-{[2-(3,3-dimethyl-ureido)-pyridin-4-ylmethyl]-amino}-benzoylamino)-2-methyl-2H-indazole-3-carboxylic acid methyl ester (53 mg, 35%) as a solid; 1H-NMR (300 MHz, d6-DMSO) 10.30 (1H, s), 8.79 (1H, s), 8.30 (1H, m), 8.15 (1H, d), 7.92-7.99 (2H, m), 7.82 (1H, s), 7.75 (1H, dd), 7.62 (1H, dd), 7.25-7.29 (1H, m), 6.93-6.96 (1H, m), 6.68 (1H, t), 6.55 (1H, d), 4.45 (2H, d), 4.41 (3H, s), 3.99 (3H, s), 2.92 (6H, s); m/z (ES+) 502 [M+H]+.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue partitioned between dichloromethane
  3. washThe organic phase was washed consecutively with saturated aqueous sodium hydrogencarbonate solution, water and brine
  4. customdried
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by chromatography on Isolute® flash silica gel (Separtis) (Gradient elution: 100% CH2Cl2 to CH2Cl2/EtOH 9:1)

Sources & evidence

ORD record
ord-5a921c1fb11a4898afacb6fa33b66490
Source dataset
uspto-grants-2011_03
Patent number
US07902229B2

Reaction notes

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