tert-Butyl 2,7-diazaspiro[3.5]nonane-2-carboxylate → 6-[2-(tert-Butoxycarbonyl)-2,7-diazaspiro[3.5]nonan-7-yl]-4-(5-methyl-1H-pyrazol-3-ylamino)-2-[2-{3-(pyrid-2-yl)isoxazol-5-yl}pyrrolidin-1-yl]pyrimidine

HRID 2105221Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:12][CH2:11][CH2:10][CH:9]2[C:13]2[O:17][N:16]=[C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=3)[CH:14]=2)[N:5]=[C:4]([NH:24][C:25]2[NH:29][N:28]=[C:27]([CH3:30])[CH:26]=2)[CH:3]=1.[C:31]([O:35][C:36]([N:38]1[CH2:41][C:40]2([CH2:46][CH2:45][NH:44][CH2:43][CH2:42]2)[CH2:39]1)=[O:37])([CH3:34])([CH3:33])[CH3:32]>O1CCOCC1>[C:31]([O:35][C:36]([N:38]1[CH2:41][C:40]2([CH2:46][CH2:45][N:44]([C:2]3[N:7]=[C:6]([N:8]4[CH2:12][CH2:11][CH2:10][CH:9]4[C:13]4[O:17][N:16]=[C:15]([C:18]5[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=5)[CH:14]=4)[N:5]=[C:4]([NH:24][C:25]4[CH:26]=[C:27]([CH3:30])[NH:28][N:29]=4)[CH:3]=3)[CH2:43][CH2:42]2)[CH2:39]1)=[O:37])([CH3:34])([CH3:32])[CH3:33]

Participants

Conditions

Temperature: 160 °C

Procedure

A mixture of 6-chloro-N-(3-methyl-1H-pyrazol-5-yl)-2-[2-(3-pyridin-2-ylisoxazol-5-yl)pyrrolidin-1-yl]pyrimidin-4-amine (Example 17) (300 mg, 0.7 mmol) and 2-(tert-butoxycarbonyl)-2,7-diazaspiro[3.5]nonane (949 mg, 4.2 mmol) in 1,4-dioxane (8 ml) was heated at 160° C. in a sealed vessel under microwave irradiation for 120 minutes. The mixture was allowed to cool and the volatiles removed by evaporation. The residue was purified by column chromatography on silica gel eluting with DCM/methanol/aqueous ammonia (100:0:0 increasing in polarity to 90:10:1) to give the product (235 mg, 55%) as a mauve solid.

Workup

temperatureto cool
customthe volatiles removed by evaporation
customThe residue was purified by column chromatography on silica gel eluting with DCM/methanol/aqueous ammonia (100:0:0 increasing in polarity to 90:10:1)

Sources & evidence

ORD record: ord-7fbc7c8d25de4f88a4e7d8ceee5e0118
Source dataset: uspto-grants-2009_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07579349B2

Reaction notes

Loading…