Ethanol → 4,6-Dichloro-1-(1,4-dioxaspiro(4.5)dec-8-yl)-1H-pyrazolo(3,4-d)pyrimidine

HRID 1093167ノート

反応式

HRID 1093167 の反応式
[O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([NH:11][NH2:12])[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.C(N(CC)CC)C.C(O)C.[Cl:23][C:24]1[N:29]=[C:28](Cl)[C:27]([CH:31]=O)=[C:26]([Cl:33])[N:25]=1>O>[Cl:33][C:26]1[N:25]=[C:24]([Cl:23])[N:29]=[C:28]2[N:11]([CH:8]3[CH2:9][CH2:10][C:5]4([O:4][CH2:3][CH2:2][O:1]4)[CH2:6][CH2:7]3)[N:12]=[CH:31][C:27]=12

参加物

6

反応物 4

HCID 702EthanolHCID 8471TriethylamineHCID 109327462,4,6-Trichloro-5-pyrimidinecarboxaldehydeHCID 574247381,4-Dioxaspiro[4.5]decan-8-ylhydrazine

生成物 1

HCID 576542784,6-Dichloro-1-(1,4-dioxaspiro(4.5)dec-8-yl)-1H-pyrazolo(3,4-d)pyrimidine収率 70.8%

試薬・触媒・溶媒 1

HCID 962Water溶媒

実験手順

(1,4-Dioxa-spiro[4.5]dec-8-yl)-hydrazine (46 g, 368 mL of above solution) was cooled in an ice bath, then triethylamine (47 mL) and ethanol (368 mL) were added. When the internal temperature reached 7.6° C., 2,4,6-trichloro-pyrimidine-5-carbaldehyde (32 g, synthesized by method of WO 02/066482) was added as a solid over 1.5 min. The internal temperature jumped to 12.6° C., and continued to rise to 17° C. during 4 min. After stirring a total of 28 min, water (367 mL) was added and the slurry was filtered. The cake was washed well twice with water (300 mL), then hexane (300 mL) and air dried over house vacuum overnight. This gave a damp cake that was washed twice with hexane (400 mL). Air-drying over house vacuum over weekend gave 35.29 g (70.8%) of 4,6-dichloro-1-(1,4-dioxa-spiro[4.5]dec-8-yl)-1H-pyrazolo[3,4-d]pyrimidine, containing ˜6.5% of 2,4,6-Trichloro-pyrimidine-5-carbaldehyde. It was important to have a minimal amount of 2,4,6-trichloro-pyrimidine-5-carbaldehyde, which consumes 2 equivalents of 8-oxa-3-aza-bicyclo[3.2.1]octane in the next step.

後処理

  1. customreached 7.6° C.
  2. customjumped to 12.6° C.
  3. additionwas added
  4. filtrationthe slurry was filtered
  5. washThe cake was washed well twice with water (300 mL)
  6. dry with materialhexane (300 mL) and air dried over house vacuum overnight
  7. customThis gave a damp cake that
  8. washwas washed twice with hexane (400 mL)
  9. customAir-drying over house vacuum over weekend

出典と根拠

ORDレコード
ord-5cee81b7c98a45b488b3408bde5352c1
出典データセット
uspto-grants-2012_03
特許番号
US08129371B2

反応ノート

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