Formamidine acetate → HCID 66589137, compound

HRID 1092199Notes

Reaction equation

HRID 1092199 reaction equation
[NH2:1][C:2]1[C:3]([C:27]([O:29][CH2:30][CH3:31])=[O:28])=[N:4][C:5]([NH:17][C@H:18]([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)[CH3:19])=[N:6][C:7]=1[NH:8][C:9]1[CH:13]=[C:12]([CH:14]2[CH2:16][CH2:15]2)[NH:11][N:10]=1.[C:32](O)(=O)C.C(N)=N>CCO>[CH:14]1([C:12]2[NH:11][N:10]=[C:9]([N:8]3[CH:32]=[N:1][C:2]4[C:7]3=[N:6][C:5]([NH:17][C@H:18]([C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)[CH3:19])=[N:4][C:3]=4[C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH:13]=2)[CH2:16][CH2:15]1

Participants

4

Reactant 2

HCID 160693Formamidine acetateHCID 86621762HCID 86621762, compound

Product 1

HCID 66589137HCID 66589137, compoundYield 9.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of (S)-ethyl 5-amino-6-(5-cyclopropyl-1H-pyrazol-3-ylamino)-2-[1-(4-fluorophenyl)ethylamino]pyrimidine-4-carboxylate (Method 47; 0.6 g, 1.4 mmol) and formamidine acetate (0.32 g, 3.1 mmol) in EtOH (20 ml) was heated to reflux for 12 hours. The reaction was then concentrated, and the resulting residue was dissolved in EtOAc (50 ml) and washed with saturated NaHCO3 solution (50 ml). The organic layer was dried, filtered, and concentrated. The resulting solid was purified by column chromatography (DCM:MeOH=20:1) to give the title compound (0.058 g, 8%). NMR (400 MHz, CD3OD) 8.48 (s, 1H), 7.45-7.41 (m, 2H), 7.03-6.99 (m, 2H), 6.25 (s, 1H), 5.12-5.03 (m, 1H), 4.50 (q, J=7.2 Hz, 2H), 2.00-1.96 (m, 1H), 1.54 (d, J=7.0 Hz, 3H), 1.44 (t, J=7.2 Hz, 3H), 1.10-1.08 (m, 2H), 0.81-0.74 (m, 2H). MS: Calcd.: 435; Found: [M+H]+ 436.

Workup

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

Sources & evidence

ORD record
ord-fa92e7a58f2c444d8c090ad5e2719ff3
Source dataset
uspto-grants-2012_03
Patent number
US08129403B2

Reaction notes

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