Triphenylphosphine → 4-[4-[2-(1-methyl-1H-pyrazol-5-yl)ethoxy]phenyl]-1-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-ol

HRID 2381133노트

반응식

HRID 2381133 반응식
CC(OC(/N=N/C(OC(C)C)=O)=O)C.[OH:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2([OH:41])[CH2:27][CH2:26][N:25]([C:28]3[CH:29]=[CH:30][C:31]4[N:32]([C:34]([C:37]([F:40])([F:39])[F:38])=[N:35][N:36]=4)[N:33]=3)[CH2:24][CH2:23]2)=[CH:18][CH:17]=1.[CH3:42][N:43]1[C:47]([CH2:48][CH2:49]OC2C=CC(C3CCN(C4CCC5N(C(C(F)(F)F)=NN=5)N=4)CC3)=CC=2)=[CH:46][CH:45]=[N:44]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[CH3:42][N:43]1[C:47]([CH2:48][CH2:49][O:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]3([OH:41])[CH2:27][CH2:26][N:25]([C:28]4[CH:29]=[CH:30][C:31]5[N:32]([C:34]([C:37]([F:40])([F:39])[F:38])=[N:35][N:36]=5)[N:33]=4)[CH2:24][CH2:23]3)=[CH:18][CH:17]=2)=[CH:46][CH:45]=[N:44]1

참가 물질

6

반응물 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 468938506-[4-[4-[2-(1-methyl-1H-pyrazol-5-yl)ethoxy]phenyl]piperidin-1-yl]-3-(trifluoromethyl)-7,8-dihydro[1,2,4]triazolo[4,3-b]pyridazineHCID 667887034-(4-Hydroxyphenyl)-1-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-ol

생성물 1

HCID 441259734-[4-[2-(1-methyl-1H-pyrazol-5-yl)ethoxy]phenyl]-1-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-ol수율 72.2%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

DIAD (0.311 mL, 1.58 mmol) was added dropwise to 4-(4-hydroxyphenyl)-1-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-ol (500 mg, 1.32 mmol), 2-(1-methyl-1H-pyrazol-5-yl)ethanol (obtained as described in Example 15, preparation of starting materials) (249 mg, 1.98 mmol) and triphenylphosphine (519 mg, 1.98 mmol) in THF (10 mL) under nitrogen. The resulting suspension was stirred at ambient temperature for 16 hours then the solvents were evaporated to give crude product. The crude product was purified by flash silica chromatography, eluting with EtOAc then a gradient of 3 to 5% MeOH in DCM. Pure fractions were evaporated to dryness to give a solid which was triturated with ether, filtered and dried to give 4-[4-[2-(1-methyl-1H-pyrazol-5-yl)ethoxy]phenyl]-1-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-ol (464 mg, 72.2%) as a solid.

후처리

  1. customthe solvents were evaporated
  2. customto give crude product
  3. customThe crude product was purified by flash silica chromatography
  4. washeluting with EtOAc
  5. customPure fractions were evaporated to dryness
  6. customto give a solid which
  7. customwas triturated with ether
  8. filtrationfiltered
  9. customdried

출처 및 근거

ORD 기록
ord-9a05e7d1b59646a8a824bef815393ca6
출처 데이터셋
uspto-grants-2012_09
특허 번호
US08258140B2

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