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

HRID 38340노트

반응식

HRID 38340 반응식
[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

참가 물질

4

반응물 3

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

생성물 1

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

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-dd7bc48294ea42608c672de111661f3f
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08524725B2

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