Formamidine acetate → HCID 68524394, compound

HRID 1437421Notes

Reaction equation

HRID 1437421 reaction equation
[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([NH:9][C:10]3[N:15]=[C:14]([NH:16][C@H:17]([C:20]4[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=4)[CH2:18][OH:19])[C:13]([N+:27]([O-])=O)=[CH:12][N:11]=3)[CH:5]=2)[CH2:3][CH2:2]1.[C:30](O)(=O)C.C(N)=N>[Pd].CCO.CCOC(C)=O.CCO>[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([NH:9][C:10]3[N:15]=[C:14]4[C:13]([N:27]=[CH:30][N:16]4[C@H:17]([C:20]4[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=4)[CH2:18][OH:19])=[CH:12][N:11]=3)[CH:5]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 2

HCID 160693Formamidine acetateHCID 68521265HCID 68521265, compound

Product 1

HCID 68524394HCID 68524394, compoundYield 61.3%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 21584252Ethanol ethylacetateSolvent

Conditions

Temperature
70 °C

Procedure

To a 25 ml round bottom flask was added palladium on activated carbon (10%, 104 mg, 0.098 mmol) and stirring bar. The flask was sealed, evacuated and refilled with hydrogen using balloon. A solution of (2R)-2-({2-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]-5-nitropyrimidin-4-yl}amino)-2-(4-fluorophenyl)ethanol (Method 1, 196 mg, 0.49 mmol) in EtOH/EtOAc (6 ml/1 ml) via syringe. The reaction mixture was stirred at room temperature for 19 hours and was filtered through paper. The filtrate was concentrated to give a pink solid. The solid was then dissolved in EtOH (4 ml) and to the mixture was added formamidine acetate (100 mg, 0.96 mmol). The reaction mixture was heated on heating block (70° C.) for 4 hours. Removal of solvent followed by flash chromatography on silica gel (10-15% MeOH in EtOAc) gave the desired product as a solid (114 mg, 61% for two steps). NMR: 0.63 (m, 2H), 0.93 (m, 2H), 1.86 (m, 1H), 4.04 (m, 1H), 4.38 (m, 1H), 5.34 (m, 1H), 5.70 (m, 1H), 6.20 (m, 1H), 7.18 (m, 2H), 7.45 (m, 2H), 8.45 (s, 1H), 8.73 (s, 1H), 9.48 (br s, 1H), 11.85 (br s, 1H).

Workup

  1. customThe flask was sealed
  2. customevacuated
  3. additionrefilled with hydrogen using balloon
  4. stirringThe reaction mixture was stirred at room temperature for 19 hours
  5. filtrationwas filtered through paper
  6. concentrationThe filtrate was concentrated
  7. customto give a pink solid
  8. temperatureThe reaction mixture was heated
  9. customRemoval of solvent

Sources & evidence

ORD record
ord-8592efbe50d941589ffdc1efc78088ea
Source dataset
uspto-grants-2009_11
Patent number
US07622482B2

Reaction notes

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