Methylamine → HCID 11154287, compound

HRID 2105200Notes

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[CH:29]=[C:28]([CH3:30])[NH:27][N:26]=2)[CH:3]=1.[CH3:31][NH2:32]>CO>[CH3:31][NH:32][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[CH:29]=[C:28]([CH3:30])[NH:27][N:26]=2)[CH:3]=1

Participants

Conditions

Temperature: 130 °C

Procedure

A mixture of 6-chloro-2-{2-[3-(pyrid-2-yl)isoxazol-5-yl]pyrrolidin-1-yl}-4-(5-methyl-1H-pyrazol-3-ylamino)pyrimidine (Example 17) (250 mg, 0.59 mmol) and methylamine (4 ml of a 2M in methanol, 8.0 mmol) was heated at 130° C. for 90 minutes in a sealed vessel under microwave irradiation. The volatiles were removed by evaporation and the residue was purified by reverse phase HPLC using a C18 column eluting with water/acetonitrile/trifluoroacetic acid (95:5:0.2 decreasing in polarity to 0:100:0.2). Product containing fractions were combined and passed through a 50 g isolute SCX-2 ion exchange column. The column was eluted with methanol to elute any neutrals, followed by 7M methanolic ammonia to elute the product. The solvent was removed by evaporation to give the title compound (126 mg, 50%) as a yellow solid.

Workup

customThe volatiles were removed by evaporation
customthe residue was purified by reverse phase HPLC
washeluting with water/acetonitrile/trifluoroacetic acid (95:5:0.2 decreasing in polarity to 0:100:0.2)
additionProduct containing fractions
washThe column was eluted with methanol
washto elute any neutrals
washto elute the product
customThe solvent was removed by evaporation

Sources & evidence

ORD record: ord-8116c073a6f74c62b48f6a1151b40af7
Source dataset: uspto-grants-2009_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07579349B2

Reaction notes

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