Triphenylphosphine → HCID 67432750, 화합물

HRID 1040158노트

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HRID 1040158 반응식
[N:1]([CH2:4][C:5]1[CH:6]=[C:7]([C:22]2[S:26][C:25]([C@@:27]3([OH:39])[CH2:32][CH2:31][C@H:30]([C:33]([O:35][CH3:36])=[O:34])[C:29]([CH3:38])([CH3:37])[CH2:28]3)=[N:24][CH:23]=2)[CH:8]=[C:9]([NH:11][C:12]2[N:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[CH:14][N:13]=2)[CH:10]=1)=[N+]=[N-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1.O>[NH2:1][CH2:4][C:5]1[CH:6]=[C:7]([C:22]2[S:26][C:25]([C@@:27]3([OH:39])[CH2:32][CH2:31][C@H:30]([C:33]([O:35][CH3:36])=[O:34])[C:29]([CH3:37])([CH3:38])[CH2:28]3)=[N:24][CH:23]=2)[CH:8]=[C:9]([NH:11][C:12]2[N:17]=[C:16]([C:18]([F:20])([F:21])[F:19])[CH:15]=[CH:14][N:13]=2)[CH:10]=1

참가 물질

5

반응물 2

HCID 11776TriphenylphosphineHCID 86658255HCID 86658255, 화합물

생성물 1

HCID 67432750HCID 67432750, 화합물수율 26.2%

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매

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온도
23 °C

실험 절차

To a solution of the product from Step 2 (220 mg, 0.392 mmol) in THF (4 ml) and water (2 ml), was added resin-bound triphenylphosphine (154 mg, 0.588 mmol, 1.5 equiv). The resulting mixture was stirred at 23° C. for 18 h. The resin-bound triphenylphosphine was removed by filtration, and the residual biphasic, orange-maroon mixture was partitioned between EtOAc (45 ml) and water (55 ml). The separated organic layer was dried over Na2SO4, filtered and concentrated. The crude orange oil was purified via reverse-phase HPLC (acetonitrile/water gradient with 0.1% TFA present). The TFA salt was converted to the free base by partitioning between EtOAc (55 ml) and saturated aqueous NaHCO3 (45 ml). The organic layer was dried over Na2SO4, filtered and concentrated. The organic layer was filtered and concentrated, yielding methyl(1S,4R)-4-{5-[3-(aminomethyl)-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl]-1,3-thiazol-2-yl}-4-hydroxy-2,2-dimethylcyclohexanecarboxylate (55 mg, 25%), as an orange oil. MS ESI: [M+H]+ m/z 536.2

후처리

  1. customThe resin-bound triphenylphosphine was removed by filtration
  2. customthe residual biphasic, orange-maroon mixture was partitioned between EtOAc (45 ml) and water (55 ml)
  3. dry with materialThe separated organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude orange oil was purified via reverse-phase HPLC (acetonitrile/water gradient with 0.1% TFA present)
  7. customby partitioning between EtOAc (55 ml) and saturated aqueous NaHCO3 (45 ml)
  8. dry with materialThe organic layer was dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. filtrationThe organic layer was filtered
  12. concentrationconcentrated

출처 및 근거

ORD 기록
ord-4c04e42c7b484574b047c5f7d1dfd5b9
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08551984B2

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