Ammonia → 5-Pyrimidinecarboxaldehyde, 4-amino-6-chloro-

HRID 880588

반응식

HRID 880588 반응식
[NH3:1].CO.[Cl:4][C:5]1[C:10]([CH:11]=[O:12])=[C:9](Cl)[N:8]=[CH:7][N:6]=1>C1(C)C=CC=CC=1>[NH2:1][C:9]1[C:10]([CH:11]=[O:12])=[C:5]([Cl:4])[N:6]=[CH:7][N:8]=1

참가 물질

5

반응물 3

HCID 222AmmoniaHCID 887MethanolHCID 8196914,6-Dichloro-5-pyrimidinecarbaldehyde

생성물 1

HCID 842305-Pyrimidinecarboxaldehyde, 4-amino-6-chloro-

시약·촉매·용매 1

HCID 1140Toluene용매

반응 조건

온도
23 °C

실험 절차

A solution of 7M NH3 in MeOH (265 mL, 1.8602 mol, 2.0 equiv) was added over 1.25 hr to a solution of 4,6-dichloropyrimidine-5-carbaldehyde (9, 163.7 g, 0.9301 mol) in toluene (3 L). The reaction temperature slowly increased from 20 to 26° C. and a yellow suspension formed. Mild cooling was applied to maintain the reaction temperature at ≦26° C. The suspension was stirred 3.5 hr at room temperature before the solids were collected by filtration. The solids were washed with EtOAc (1 L). The filtrate was concentrated under reduced pressure, and the solids were triturated with toluene/heptane (2:1 v/v, 600 mL), filtered and dried to give 71.1 g of 4-amino-6-chloropyrimidine-5-carbaldehyde (10) as a yellow solid. The original solid filtered from the reaction mixture contained additional 10. The product was extracted from the filtered solid by stirring in EtOAc (1.25 L) for 1.5 hr, filtering, then stirring in THF (750 mL) for 1 hr and filtering. Both EtOAc and THF filtrates were concentrated under reduced pressure, and the resulting solids were triturated with toluene/heptane (2:1 v/v, 450 mL), filtered and dried to give an additional 44.1 g of 4-amino-6-chloropyrimidine-5-carbaldehyde (10) as yellow solids. The combined yield of 4-amino-6-chloropyrimidine-5-carbaldehyde (10, 115.2 g, 146.5 g theoretical) was 78.6%. For 10: 1H NMR (DMSO-d6, 300 MHz) δ ppm 10.23 (s, 1H), 8.71 (bs, 1H), 8.55 (bs, 1H), 8.39 (s, 1H); C5H4ClN3O (MW, 157.56), LCMS (EI) m/e 158 (M++H).

후처리

  1. customa yellow suspension formed
  2. temperatureMild cooling
  3. temperatureto maintain the reaction temperature at ≦26° C
  4. filtrationwere collected by filtration
  5. washThe solids were washed with EtOAc (1 L)
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customthe solids were triturated with toluene/heptane (2:1 v/v, 600 mL)
  8. filtrationfiltered
  9. customdried

출처 및 근거

ORD 기록
ord-78a8111054cb4fbc8e1c33e88eae18a2
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08993582B2

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