Formamidine acetate → (2R)-2-[9-(5-Cyclopropyl-1H-pyrazol-3-yl)-6-methyl-9H-purin-2-ylamino]-2-(4-fluorophenyl)ethanol

HRID 1092197Notes

Reaction equation

HRID 1092197 reaction equation
[NH2:1][C:2]1[C:3]([NH:20][C:21]2[CH:25]=[C:24]([CH:26]3[CH2:28][CH2:27]3)[NH:23][N:22]=2)=[N:4][C:5]([NH:9][C@H:10]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)[CH2:11][OH:12])=[N:6][C:7]=1[CH3:8].[C:29](O)(=O)C.C(N)=N>CCO>[CH:26]1([C:24]2[NH:23][N:22]=[C:21]([N:20]3[CH:29]=[N:1][C:2]4[C:3]3=[N:4][C:5]([NH:9][C@H:10]([C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=3)[CH2:11][OH:12])=[N:6][C:7]=4[CH3:8])[CH:25]=2)[CH2:28][CH2:27]1

Participants

4

Reactant 2

HCID 160693Formamidine acetateHCID 66589221(R)-2-[5-amino-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6-methylpyrimidin-2-ylamino]-2-(4-fluorophenyl)ethanol

Product 1

HCID 11696847(2R)-2-[9-(5-Cyclopropyl-1H-pyrazol-3-yl)-6-methyl-9H-purin-2-ylamino]-2-(4-fluorophenyl)ethanolYield 35%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of (R)-2-[5-amino-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6-methylpyrimidin-2-ylamino]-2-(4-fluorophenyl)ethanol (Method 40; 0.3 g, 0.8 mmol) and formamidine acetate (0.2 g, 1.6 mmol) in EtOH (8 ml) was heated to reflux for 12 hours. The reaction was then concentrated, dissolved in DCM (50 ml), and washed with saturated NaHCO3 solution (50 ml). The organic layer was then dried, filtered, and concentrated. The resulting solid was purified by column chromatography (DCM:MeOH=20:1) to give the title compound (0.11 g, 35%). NMR (400 MHz, CD3OD) 8.32 (s, 1H), 7.46-7.43 (m, 2H), 7.06-7.02 (m, 2H), 6.24 (s, 1H), 5.10-5.02 (m, 1H), 3.87-3.75 (m, 2H), 2.61 (s, 3H), 1.99-1.96 (m, 1H), 1.10-1.08 (m, 2H), 0.80-0.75 (m, 2H). MS: Calcd.: 393; Found: [M+H]+ 394.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 12 hours
  3. concentrationThe reaction was then concentrated
  4. dissolutiondissolved in DCM (50 ml)
  5. washwashed with saturated NaHCO3 solution (50 ml)
  6. customThe organic layer was then dried
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe resulting solid was purified by column chromatography (DCM:MeOH=20:1)

Sources & evidence

ORD record
ord-75aa564c95a64ae8b8a08c7b2012737a
Source dataset
uspto-grants-2012_03
Patent number
US08129403B2

Reaction notes

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