2-Amino-2-methyl-1-propanol → HCID 135730640, compound

HRID 354180Notes

Reaction equation

HRID 354180 reaction equation
[CH2:1]([O:5][C:6]1[C:14]([C:15]2[NH:16][C:17](=[O:28])[C:18]3[C:19](=[C:21]([CH2:25][CH2:26][CH3:27])[N:22]([CH3:24])[N:23]=3)[N:20]=2)=[CH:13][C:9]([C:10](O)=[O:11])=[CH:8][N:7]=1)[CH:2]([CH3:4])[CH3:3].C(Cl)(=O)C(Cl)=O.[NH2:35][C:36]([CH3:40])([CH3:39])[CH2:37]O.C(N(C(C)C)CC)(C)C.S(Cl)(Cl)=O>ClCCl.CN(C)C=O>[CH3:37][C:36]1([CH3:40])[CH2:39][O:11][C:10]([C:9]2[CH:13]=[C:14]([C:15]3[NH:16][C:17](=[O:28])[C:18]4[C:19](=[C:21]([CH2:25][CH2:26][CH3:27])[N:22]([CH3:24])[N:23]=4)[N:20]=3)[C:6]([O:5][CH2:1][CH:2]([CH3:3])[CH3:4])=[N:7][CH:8]=2)=[N:35]1

Participants

8

Reactant 5

HCID 118072-Amino-2-methyl-1-propanolHCID 24386Thionyl ChlorideHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 135730583HCID 135730583, compound

Product 1

HCID 135730640HCID 135730640, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent4×

Procedure

6-Isobutoxy-5-(2-methyl-7-oxo-3-propyl-6,7-dihydro-2H-pyrazolo[4,3-d]pyrimidin-5-yl)nicotinic acid (Example 24) (200 mg, 0.52 mmol) was dissolved in dichloromethane and oxalyl chloride (0.18 mL, 2.8 mmol) was added followed by 1 drop of N,N-dimethylformamide. The mixture was stirred for 2 h and the solvent was then removed in vacuo, azeotroping with further dichloromethane. A dichloromethane solution of the acid chloride was then added to a solution of 2-amino-2-methyl-1-propanol (0.05 mL, 0.52 mmol) and diisopropylethylamine (0.09 mL, 0.62 mmol) in dichloromethane and the mixture stirred for 2 h. The reaction mixture was diluted with further dichloromethane and washed with a 1 N solution of citric acid, followed by brine. The organics were dried (MgSO4) and concentrated in vacuo. The residue was redissolved in dichloromethane and thionyl chloride (0.05 mL, 0.62 mmol) was added. After 2 h the solution was washed with water then sodium bicarbonate solution. The organic phase was dried and concentrated. The crude residue was purified by flash column chromatography (50% ethyl acetate:pentane as eluant) to give the product.

Workup

  1. customthe solvent was then removed in vacuo
  2. customazeotroping with further dichloromethane
  3. stirringthe mixture stirred for 2 h
  4. washwashed with a 1 N solution of citric acid
  5. dry with materialThe organics were dried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. dissolutionThe residue was redissolved in dichloromethane
  8. washAfter 2 h the solution was washed with water
  9. customThe organic phase was dried
  10. concentrationconcentrated
  11. customThe crude residue was purified by flash column chromatography (50% ethyl acetate:pentane as eluant)
  12. customto give the product

Sources & evidence

ORD record
ord-a7ec41cc862546cbae506c6c2491a2c2
Source dataset
uspto-grants-2004_06
Patent number
US06756373B1

Reaction notes

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