2-Aminopyrimidine → HCID 22598938, compound

HRID 2252465Notes

Reaction equation

HRID 2252465 reaction equation
O=[CH:2][CH2:3][CH2:4][N:5]1[C:13]2[C:8](=[CH:9][C:10]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:11][CH:12]=2)[CH:7]=[N:6]1.[NH2:19][C:20]1[N:25]=[CH:24][CH:23]=[CH:22][N:21]=1.S([O-])([O-])(=O)=O.[Mg+2].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.O>[N:21]1[CH:22]=[CH:23][CH:24]=[N:25][C:20]=1[NH:19][CH2:2][CH2:3][CH2:4][N:5]1[C:13]2[C:8](=[CH:9][C:10]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:11][CH:12]=2)[CH:7]=[N:6]1

Participants

8

Reactant 5

HCID 79782-AminopyrimidineHCID 24083Sulfuric acid magnesium salt (1:1)HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 10538372HCID 10538372, compound

Product 1

HCID 22598938HCID 22598938, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent2×

Procedure

Ethyl 1-(3-oxopropyl)-1H-indazole-5-carboxylate (1.0 g, 4.06 mmol, prepared as described in Jadhav et al, U.S. Pat. No. 5,760,028) was dissolved in toluene (15 mL) and 2-aminopyrimidine (463 mg, 4.9 mmol) added, along with anhydrous magnesium sulfate (2.44 g, 20 mmol) under nitrogen. The mixture was vigorously stirred for six hours, filtered under nitrogen, the solids washed (10 mL toluene), and the filtrate treated with sodium triacetoxyborohydride (8.6 g, 40 mmol). The reaction was stirred under nitrogen for 18 hours, diluted with toluene (25 mL), and poured into water (100 mL). Saturated sodium bicarbonate solution (80 mL) was added to adjust pH>8. The layers were separated and the aqueous layer extracted with three portions of ethyl acetate. The combined organics were washed with saturated bicarbonate solution, water, and brine, dried over sodium sulfate, filtered, and concentrated under vacuum to afford a golden oil (1.3 g). This purified by preparative HPLC (Vydac C18, 21.2 mm×25 cm, 90% acetonitrile/water/0.1% TFA; 10-70% B over 30 minutes). The product fractions were frozen and lyophilized to afford the desired product as a white powder (520 mg, 40%). LRMS (ES): 326.2 ([M+H]+. HRMS: Calculated for C17H20N5O2: 326.1617. Found: 326.1605. 1HNMR (600.1343 MHz, CDCl3): 9.68 (bs, 1H), 8.58 (m, 1H), 8.49 (s, 1H), 8.12 (s, 1H), 8.08 (m, 1H), 8.03, (t, 1H), 7.50 (d, 1H), 6.73 (t, 1H), 4.55 (m, 2H), 4.39 (q, 2H), 3.36 (m, 2H), 2.35 (m, 2H), 1.41 (t, 3H).

Workup

  1. filtrationfiltered under nitrogen
  2. washthe solids washed (10 mL toluene)
  3. stirringThe reaction was stirred under nitrogen for 18 hours
  4. customThe layers were separated
  5. extractionthe aqueous layer extracted with three portions of ethyl acetate
  6. washThe combined organics were washed with saturated bicarbonate solution, water, and brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-2ce435ad86624f3e97674e2b7a6ca9b3
Source dataset
uspto-grants-2008_01
Patent number
US07321045B2

Reaction notes

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