Triethylamine → 3-(6-chloro-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane

HRID 1093171Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([CH:9]=O)=[C:4](Cl)[N:3]=1.[NH2:12][NH2:13].C(N(CC)CC)C.Cl.[CH:22]12[O:29][CH:26]([CH2:27][CH2:28]1)[CH2:25][NH:24][CH2:23]2>ClCCl.C(O)C>[Cl:1][C:2]1[N:3]=[C:4]2[NH:12][N:13]=[CH:9][C:5]2=[C:6]([N:24]2[CH2:23][CH:22]3[O:29][CH:26]([CH2:27][CH2:28]3)[CH2:25]2)[N:7]=1

Participants

Conditions

Temperature: -78 °C

Procedure

A nearly homogeneous suspension of 2,4,6-trichloro-pyrimidine-5-carbaldehyde (example 1, Scheme 28, 2.1 g, 10 mmol) in dichloromethane/ethanol (8:2, 100 mL) was cooled to −78° C. in a dry-ice/acetone bath. Anhydrous hydrazine (0.31 mL, 10 mmol) was added in drops via syringe, followed by triethylamine (4 mL), also via dropwise addition. The cooling bath was removed and after one hour, the opaque maroon mixture was treated with 8-oxa-3-aza-bicyclo[3.2.1]octane hydrochloride (1.4 g, 9.4 mmol), followed by triethylamine (2 mL). The mixture was allowed to stir overnight. The maroon solid was collected by Buchner filtration, washed with ethanol, and then dried under house vacuum to give 3-(6-chloro-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane (0.82 g, 31%). MS (ES+): 266.2, 268.2 (M+H)+

Workup

customThe cooling bath was removed and after one hour
filtrationThe maroon solid was collected by Buchner filtration
washwashed with ethanol
customdried under house vacuum

Sources & evidence

ORD record: ord-289a5910cb194bb8b14cab3de9182d57
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08129371B2

Reaction notes

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