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

반응식

HRID 720689 반응식
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

참가 물질

8

반응물 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

생성물 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-amide수율 82.2%

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6344Dichloromethane용매

반응 조건

온도
0 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-314541c9432d4781942a7834c8a30caf
출처 데이터셋
uspto-grants-2006_11
특허 번호
US07135475B2

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