Triethylamine → 1,3,5-trimethyl-1H-pyrazole-4-carboxylic acid {4-[3-cyclopropylmethyl-1-(2-fluorobenzyl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylmethyl]-phenyl}-ethyl-amide

HRID 720689

反応式

HRID 720689 の反応式
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:20][N:21]1[C:25]([CH3:26])=[C:24]([C:27]([OH:29])=O)[C:23]([CH3:30])=[N:22]1.ClN1C(=O)CCC1=O.[CH:39]1([CH2:42][N:43]2[C:51]3[N:50]=[C:49]([CH2:52][C:53]4[CH:58]=[CH:57][C:56]([NH:59][CH2:60][CH3:61])=[CH:55][CH:54]=4)[NH:48][C:47]=3[C:46](=[O:62])[N:45]([CH2:63][C:64]3[CH:69]=[CH:68][CH:67]=[CH:66][C:65]=3[F:70])[C:44]2=[O:71])[CH2:41][CH2:40]1.C(N(CC)CC)C>ClCCl.CN(C)C1C=CN=CC=1>[CH:39]1([CH2:42][N:43]2[C:51]3[N:50]=[C:49]([CH2:52][C:53]4[CH:54]=[CH:55][C:56]([N:59]([CH2:60][CH3:61])[C:27]([C:24]5[C:23]([CH3:30])=[N:22][N:21]([CH3:20])[C:25]=5[CH3:26])=[O:29])=[CH:57][CH:58]=4)[NH:48][C:47]=3[C:46](=[O:62])[N:45]([CH2:63][C:64]3[CH:69]=[CH:68][CH:67]=[CH:66][C:65]=3[F:70])[C:44]2=[O:71])[CH2:41][CH2:40]1

参加物

8

反応物 5

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 31398ChlorosuccinimideHCID 7365141,3,5-trimethyl-1H-pyrazole-4-carboxylic acidHCID 218918193-Cyclopropylmethyl-8-[4-(ethyl-amino)-benzyl]-1-(2-fluorobenzyl)-3,7-dihydro-purine-2,6-dione

生成物 1

HCID 587392471,3,5-trimethyl-1H-pyrazole-4-carboxylic acid {4-[3-cyclopropylmethyl-1-(2-fluorobenzyl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylmethyl]-phenyl}-ethyl-amide収率 82.2%

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

A suspension of triphenylphosphine (59.3 mg, 0.226 mmol) and 1,3,5-trimethyl-1H-pyrazole-4-carboxylic acid (SALOR) (26.8 mg, 0.174 mmol) in dichloromethane was cooled to 0° C. and N-chlorosuccinimide added. The mixture was stirred at 0° C. for 0.5 h then ambient temperature for an additional 0.5 h. 3-Cyclopropylmethyl-8-[4-(ethyl-amino)-benzyl]-1-(2-fluorobenzyl)-3,7-dihydro-purine-2,6-dione (93.4 mg, 0.209 mmol) was added followed by triethylamine (30.2 mg, 0.226 mmol) and 4-dimethylaminopyridine (a few crystals). The reaction was left to stir at ambient temperature overnight before washing with 1M aqueous hydrochloric acid, saturated aqueous sodium bicarbonate, drying the organic extract (sodium sulfate) and concentrating in vacuo. Purification by chromatography using silica eluted with 5:9 methanol/dichloromethane gave the product as a colorless solid (83.5 mg, 69%). MS, m/z(M+H)=584.2787.

後処理

  1. waitambient temperature for an additional 0.5 h
  2. waitThe reaction was left
  3. stirringto stir at ambient temperature overnight
  4. washbefore washing with 1M aqueous hydrochloric acid, saturated aqueous sodium bicarbonate
  5. customdrying the
  6. extractionorganic extract (sodium sulfate)
  7. concentrationconcentrating in vacuo
  8. customPurification by chromatography
  9. washeluted with 5:9 methanol/dichloromethane

出典と根拠

ORDレコード
ord-314541c9432d4781942a7834c8a30caf
出典データセット
uspto-grants-2006_11
特許番号
US07135475B2

関連ノート

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