Methylamine → Methyl-carbamic acid 2-[4-amino-5-(5-chloro-2-isopropyl-4-methoxy-phenoxy)-pyrimidin-2-ylamino]-propyl ester

HRID 38340Notes

Reaction equation

HRID 38340 reaction equation
[NH2:1][C:2]1[C:7]([O:8][C:9]2[CH:14]=[C:13]([Cl:15])[C:12]([O:16][CH3:17])=[CH:11][C:10]=2[CH:18]([CH3:20])[CH3:19])=[CH:6][N:5]=[C:4]([NH:21][C@H:22]([CH3:25])[CH2:23][OH:24])[N:3]=1.[CH3:26][NH2:27].C1[CH2:32][O:31]CC1>>[NH2:1][C:2]1[C:7]([O:8][C:9]2[CH:14]=[C:13]([Cl:15])[C:12]([O:16][CH3:17])=[CH:11][C:10]=2[CH:18]([CH3:20])[CH3:19])=[CH:6][N:5]=[C:4]([NH:21][CH:22]([CH3:25])[CH2:23][O:24][C:32](=[O:31])[NH:27][CH3:26])[N:3]=1

Participants

4

Reactant 3

HCID 6329MethylamineHCID 8028TetrahydrofuranHCID 161191702-[4-Amino-5-(5-chloro-2-isopropyl-4-methoxy-phenoxy)-pyrimidin-2-ylamino]-(R)-propan-1-ol

Product 1

HCID 16119173Methyl-carbamic acid 2-[4-amino-5-(5-chloro-2-isopropyl-4-methoxy-phenoxy)-pyrimidin-2-ylamino]-propyl ester

Procedure

1,1-Carbonyldiimidazole (0.97 g, 6 mmol) was added to a solution of 2-[4-Amino-5-(5-chloro-2-isopropyl-4-methoxy-phenoxy)-pyrimidin-2-ylamino]-(R)-propan-1-ol from Example 4 (0.22 g, 0.6 mmol) in 20 mL of THF at room temperature. The mixture was stirred for 2 hours and methylamine (3 mL, 2M/THF, 0.6 mmol) was added. The reaction mixture was stirred overnight and concentrated under reduced pressure, diluted with water (75 mL), and extracted with EtOAc (2×75 mL). The organic phase was washed with Brine and dried with MgSO4. The solution was filtered and concentrated. The residue was purified on two Silica preparative TLC plates (20×40 cm) eluting with 5% MeOH/dichloromethane affording 143 mg of methyl-carbamic acid 2-[4-amino-5-(5-chloro-2-isopropyl-4-methoxy-phenoxy)-pyrimidin-2-ylamino]-propyl ester: MS (M+H); 424: MP; 63.5-69.4° C.

Workup

  1. stirringThe reaction mixture was stirred overnight
  2. concentrationconcentrated under reduced pressure
  3. additiondiluted with water (75 mL)
  4. extractionextracted with EtOAc (2×75 mL)
  5. washThe organic phase was washed with Brine
  6. dry with materialdried with MgSO4
  7. filtrationThe solution was filtered
  8. concentrationconcentrated
  9. customThe residue was purified on two Silica preparative TLC plates (20×40 cm)
  10. washeluting with 5% MeOH/dichloromethane affording 143 mg of methyl-carbamic acid 2-[4-amino-5-(5-chloro-2-isopropyl-4-methoxy-phenoxy)-pyrimidin-2-ylamino]-propyl ester

Sources & evidence

ORD record
ord-dd7bc48294ea42608c672de111661f3f
Source dataset
uspto-grants-2013_09
Patent number
US08524725B2

Reaction notes

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