Methyl iodide → HCID 71515783, compound

HRID 574645Notes

Reaction equation

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

Participants

Conditions

Temperature: 25 °C

Procedure

According to Scheme 10: To a solution of 3-[5-acetyl-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 (11t) (0.10 g, 0.276 mmol) in dry DMF (1 ml) at −10° C. NaHMDS (50 mg) was added. After 5 min iodomethane (39 mg, 0.276 mmol) was added and the mixture was allowed to warm to 25° C. After 90 min the mixture was cooled to −10° C. and the same amount of both NaHMDS and iodomethane was added again. After stirring overnight the mixture was purified by reverse phase HPLC (CH3CN/water gradient with 0.1% trifluoroacetic acid) to give 27 mg of 3-[5-acetyl-1-((1R,2R)-4,6-difluoro-2-methoxy-indan-1-yl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile (16a). Rt=1.29 min (LC method 4). Detected mass: 449.32 [M+H+]

Workup

customat −10° C
temperatureAfter 90 min the mixture was cooled to −10° C.
customwas purified by reverse phase HPLC (CH3CN/water gradient with 0.1% trifluoroacetic acid)

Sources & evidence

ORD record: ord-42eccdc5b69c4590a68bde101fe1d1db
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09034897B2

Reaction notes

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