Methylamine → 2-(methylamino)-N-[6-(2-phenylethynyl)-4-(pyridin-4-yl)-5-(pyrimidin-5-yl)pyridin-2-yl]propanamide

HRID 923671Notes

Reaction equation

[C:1]1([C:7]#[C:8][C:9]2[N:14]=[C:13]([NH2:15])[CH:12]=[C:11]([C:16]3[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=3)[C:10]=2[C:22]2[CH:23]=[N:24][CH:25]=[N:26][CH:27]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C[CH2:29][N:30](CC)CC.Br[CH:36]([CH3:40])[C:37](Br)=[O:38].CN>CN(C1C=CN=CC=1)C.O1CCOCC1>[CH3:29][NH:30][CH:36]([CH3:40])[C:37]([NH:15][C:13]1[CH:12]=[C:11]([C:16]2[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=2)[C:10]([C:22]2[CH:23]=[N:24][CH:25]=[N:26][CH:27]=2)=[C:9]([C:8]#[C:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[N:14]=1)=[O:38]

Participants

Conditions

Temperature: 0 °C

Procedure

A mixture of 6-(2-phenylethynyl)-4-(pyridin-4-yl)-5-(pyrimidin-5-yl)pyridin-2-amine G9 (72 mg, 0.21 mmol), DMAP (0.05 mg, 4 μmol) and Et3N (43 μl, 0.31 mmol) in dioxane (4.3 ml) is stirred at 0° C. for 15 minutes. 2-bromo-propionyl bromide (33 μl, 0.31 mmol) is added dropwise and the mixture stirred at RT for 1 h. The mixture is heated to 90° C. and stirred for 16 h. Et3N (43 μl, 0.31 mmol) and 2-Bromo-propionyl bromide (33 μl, 0.31 mmol) is added and the mixture stirred for another 3 h. The mixture is cooled to RT, methylamine (2 mol/l solution in THF, 1.03 ml, 2.06 mmol) is added and the mixture stirred for 17 h. The mixture is concentrated in vacuo and the product purified by RP HPLC. Yield: 7.6 mg (9%). HPLC-MS: M+H=435; tR=.2.75 min (METHOD—6).

Workup

stirringthe mixture stirred at RT for 1 h
temperatureThe mixture is heated to 90° C.
stirringstirred for 16 h
stirringthe mixture stirred for another 3 h
temperatureThe mixture is cooled to RT
stirringthe mixture stirred for 17 h
concentrationThe mixture is concentrated in vacuo
customthe product purified by RP HPLC
custom2.75 min (METHOD—6)

Sources & evidence

ORD record: ord-18940d868deb41fc801e585ee2b40ee0
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09278978B2

Reaction notes

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