Water → HCID 71515595, compound

HRID 574640Notes

Reaction equation

[F:1][C:2]([F:23])([F:22])[O:3][C:4]1[CH:5]=[C:6]([C:10]2[C:14]3[CH2:15][N:16]([C:19](=[O:21])[CH3:20])[CH2:17][CH2:18][C:13]=3[NH:12][N:11]=2)[CH:7]=[CH:8][CH:9]=1.[F:24][C:25]1[CH:26]=[C:27]([F:35])[C:28]2[CH2:29][C@H:30]3[O:34][C@H:31]3[C:32]=2[CH:33]=1.C([O-])([O-])=O.[K+].[K+].O>CC#N>[F:35][C:27]1[CH:26]=[C:25]([F:24])[CH:33]=[C:32]2[C:28]=1[CH2:29][C@@H:30]([OH:34])[C@@H:31]2[N:12]1[C:13]2[CH2:18][CH2:17][N:16]([C:19](=[O:21])[CH3:20])[CH2:15][C:14]=2[C:10]([C:6]2[CH:7]=[CH:8][CH:9]=[C:4]([O:3][C:2]([F:1])([F:22])[F:23])[CH:5]=2)=[N:11]1

Participants

Conditions

Temperature: 50 °C

Procedure

A mixture of 1-[3-(3-trifluoromethoxy-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone (3e) (0.461 mmol), 0.44 g, 2.65 mmol), (1aS,6aR)-3,5-difluoro-6,6a-dihydro-1aH-1-oxa-cyclopropa[a]indene (6b) (0.077 g, 0.461 mmol) and K2CO3 (127 mg, 0.922 mmol) in 5 ml CH3CN was stirred at 50° C. for 24 h. Water was added, the mixture was extracted 3 times with CH2Cl2, the combined organic layers were dried over MgSO4, filtrated and the solution was evaporated to dryness. The crude product was purified by reverse phase HPLC (CH3CN/water gradient with 0.1% trifluoroacetic acid) to give 53 mg of 1-[1-((1R,2R)-4,6-difluoro-2-hydroxy-indan-1-yl)-3-(3-trifluoromethoxy-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone (11a).

Workup

extractionthe mixture was extracted 3 times with CH2Cl2
dry with materialthe combined organic layers were dried over MgSO4
filtrationfiltrated
customthe solution was evaporated to dryness
customThe crude product was purified by reverse phase HPLC (CH3CN/water gradient with 0.1% trifluoroacetic acid)

Sources & evidence

ORD record: ord-1ec368fe5b1f4584843ad22033cd8cf6
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09034897B2

Reaction notes

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