Hydrochloric Acid → 3-(((1R,2R)-2-amino-3,3-difluorocyclohexyl)amino)-5-((3-(pyrimidin-2-yl)phenyl)amino)-1,2,4-triazine-6-carboxamide

HRID 577420ノート

反応式

HRID 577420 の反応式
CS[C:3]1[N:4]=[N:5][C:6]([C:22]([NH2:24])=[O:23])=[C:7]([NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]3[N:21]=[CH:20][CH:19]=[CH:18][N:17]=3)[CH:11]=2)[N:8]=1.C1C=C(Cl)C=C(C(OO)=O)C=1.CCN(C(C)C)C(C)C.Cl.Cl.[F:47][C:48]1([F:56])[CH2:53][CH2:52][CH2:51][C@@H:50]([NH2:54])[C@H:49]1[NH2:55].C(O)(C(F)(F)F)=O.Cl>CN1C(=O)CCC1>[NH2:55][C@H:49]1[C:48]([F:56])([F:47])[CH2:53][CH2:52][CH2:51][C@H:50]1[NH:54][C:3]1[N:4]=[N:5][C:6]([C:22]([NH2:24])=[O:23])=[C:7]([NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]3[N:21]=[CH:20][CH:19]=[CH:18][N:17]=3)[CH:11]=2)[N:8]=1

参加物

8

反応物 6

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 70297m-Chloroperbenzoic acidHCID 81531DiisopropylethylamineHCID 86685557(1R,2R)-3,3-difluorocyclohexane-1,2-diamine dihydrochlorideHCID 867064133-(Methylthio)-5-(3-(pyrimidin-2-yl)phenylamino)-1,2,4-triazine-6-carboxamide

生成物 1

HCID 727032273-(((1R,2R)-2-amino-3,3-difluorocyclohexyl)amino)-5-((3-(pyrimidin-2-yl)phenyl)amino)-1,2,4-triazine-6-carboxamide収率 66.1%

試薬・触媒・溶媒 1

HCID 13387N-methyl-2-pyrrolidone溶媒

実験手順

3-(Methylthio)-5-(3-(pyrimidin-2-yl)phenylamino)-1,2,4-triazine-6-carboxamide (40 mg, 0.12 mmol) was dissolved in 4 mL NMP. To it was added mCPBA (77%) (108 mg, 0.48 mmol). The mixture was stirred at RT for 1 h. To it was added DIEA (0.21 mL, 1.20 mmol) and (1R,2R)-3,3-difluorocyclohexane-1,2-diamine dihydrochloride (53 mg, 0.24 mmol). The mixture was stirred at 80° C. for 1 h. It was cooled to RT, acidified with TFA (0.3 mL) and subjected to reverse phase preparative HPLC to isolate the title compound (35 mg) as HCl salt. MS found for C20H21F2N9O as (M+H)+ 442.5. UV: λ=240 nm. Proton NMR: (CD3OD) δ 8.94-8.92 (3H, m), 8.41 (1H, d, J=8.0 Hz), 7.79 (1H, d, J=8.0 Hz), 7.64 (1H, t, J=8.0 Hz), 7.45 (1H, t, J=4.8 Hz), 4.90 (1H, m), 4.13 (1H, m), 2.24-1.82 (6H, m) ppm.

後処理

  1. stirringThe mixture was stirred at 80° C. for 1 h
  2. temperatureIt was cooled to RT

出典と根拠

ORDレコード
ord-401d987570874833b73dd58a3b875d23
出典データセット
uspto-grants-2015_05
特許番号
US09040530B2

反応ノート

読み込み中…