Water → HCID 66589241, compound

HRID 1092198Notes

Reaction equation

HRID 1092198 reaction equation
[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([NH:9][C:10]3[C:15]([NH2:16])=[CH:14][N:13]=[C:12]([NH:17][C@H:18]([C:20]4[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=4)[CH3:19])[N:11]=3)[CH:5]=2)[CH2:3][CH2:2]1.[N:27]([O-])=O.[Na+].O>C(O)(=O)C>[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([N:9]3[C:10]4[N:11]=[C:12]([NH:17][C@H:18]([C:20]5[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=5)[CH3:19])[N:13]=[CH:14][C:15]=4[N:16]=[N:27]3)[CH:5]=2)[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 962WaterHCID 23668193Sodium NitriteHCID 67478794HCID 67478794, compound

Product 1

HCID 66589241HCID 66589241, compoundYield 41.2%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a solution of (S)-N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-[1-(4-fluorophenyl)ethyl]pyrimidine-2,4,5-triamine (Method 8; 0.04 g, 0.1 mmol) in aqueous acetic acid (5%, 3 ml) was slowly added an aqueous NaNO2 solution (0.008 g, 0.1 mmol, 1 ml H2O). The reaction was allowed to stir for an additional 5 minutes, treated with water (10 ml), and extracted with DCM (3×25 ml). The combined organic layer was washed with saturated NaHCO3 solution (50 ml), dried, filtered, and concentrated. The resulting solid was purified by column chromatography (DCM:MeOH=15:1) to give the title compound (0.015 g, 40%). NMR (400 MHz, CD3OD) 9.05 (s, 1H), 7.44-7.41 (m, 2H), 7.03-6.99 (m, 2H), 6.23 (s, 1H), 5.16-5.07 (m, 1H), 2.03-2.00 (m, 1H), 1.55 (d, J=6.8 Hz, 3H), 1.11-1.09 (m, 2H), 0.85-0.80 (m, 2H). MS: Calcd.: 364; Found: [M+H]+ 365.

Workup

  1. extractionextracted with DCM (3×25 ml)
  2. washThe combined organic layer was washed with saturated NaHCO3 solution (50 ml)
  3. customdried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe resulting solid was purified by column chromatography (DCM:MeOH=15:1)

Sources & evidence

ORD record
ord-d1e81aa98fa64d0ba604b0880df46498
Source dataset
uspto-grants-2012_03
Patent number
US08129403B2

Reaction notes

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