Triethylamine → HCID 71515593, compound

HRID 574644Notes

Reaction equation

[F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]2[C:3]=1[CH2:4][C@@H:5]([OH:29])[C@@H:6]2[N:12]1[C:20]2[CH2:19][CH2:18][NH:17][CH2:16][C:15]=2[C:14]([C:21]2[CH:22]=[C:23]([CH:26]=[CH:27][CH:28]=2)[C:24]#[N:25])=[N:13]1.C(N(CC)CC)C.[C:37](Cl)(=[O:40])[CH2:38][CH3:39].C([O-])(O)=O.[Na+]>C(Cl)Cl>[F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]2[C:3]=1[CH2:4][C@@H:5]([OH:29])[C@@H:6]2[N:12]1[C:20]2[CH2:19][CH2:18][N:17]([C:37](=[O:40])[CH2:38][CH3:39])[CH2:16][C:15]=2[C:14]([C:21]2[CH:22]=[C:23]([CH:26]=[CH:27][CH:28]=2)[C:24]#[N:25])=[N:13]1

Participants

Conditions

Temperature: 2.5 °C

Procedure

According to Scheme 9: To a solution of 3-[1-((1R,2R)-4,6-difluoro-2-hydroxy-indan-1-yl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile (13c) (0.05 g, 0.127 mmol) in CH2Cl2 (2 ml) at 0° C. triethylamine (19 mg, 0.191 mmol) and propionyl chloride (13 mg, 0.140 mmol) was added and the mixture was stirred for 30 min at 0-5° C. After addition of aqueous saturated NaHCO3 (2 ml), the mixture was extracted with CH2Cl2 (10 ml), the organic layer was dried over Na2SO4, solvents were evaporated in vacuo and the crude product was purified by reverse phase HPLC (CH3CN/water gradient with 0.1% trifluoroacetic acid) to give 15 mg of 3-[1-((1R,2R)-4,6-difluoro-2-hydroxy-indan-1-yl)-5-propionyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile (14a).

Workup

extractionthe mixture was extracted with CH2Cl2 (10 ml)
dry with materialthe organic layer was dried over Na2SO4, solvents
customwere evaporated in vacuo
customthe crude product was purified by reverse phase HPLC (CH3CN/water gradient with 0.1% trifluoroacetic acid)

Sources & evidence

ORD record: ord-16520adfefd1433486d926ea2caaf8f2
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09034897B2

Reaction notes

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