Diisopropylethylamine → 3-((3S,9aS)-8-(2-(2-aminopyrimidin-5-yl)-2,2-difluoroacetyl)octahydropyrazino[2,1-c][1,4]oxazin-3-yl)-6-fluoro-2-methylbenzonitrile

HRID 1502178ノート

反応式

HRID 1502178 の反応式
[F:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([CH3:10])[C:5]([C@@H:11]2[O:16][CH2:15][C@@H:14]3[CH2:17][NH:18][CH2:19][CH2:20][N:13]3[CH2:12]2)=[CH:4][CH:3]=1.[NH2:21][C:22]1[N:27]=[CH:26][C:25]([C:28]([F:33])([F:32])[C:29](O)=[O:30])=[CH:24][N:23]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CO>[NH2:21][C:22]1[N:23]=[CH:24][C:25]([C:28]([F:33])([F:32])[C:29]([N:18]2[CH2:19][CH2:20][N:13]3[C@H:14]([CH2:15][O:16][C@@H:11]([C:5]4[C:6]([CH3:10])=[C:7]([C:2]([F:1])=[CH:3][CH:4]=4)[C:8]#[N:9])[CH2:12]3)[CH2:17]2)=[O:30])=[CH:26][N:27]=1

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 712721096-fluoro-2-methyl-3-((3S,9aS)-octahydropyrazino[2,1-c][1,4]oxazin-3-yl)benzonitrileHCID 896192612-(2-Aminopyrimidin-5-yl)-2,2-difluoroacetic acid

生成物 1

HCID 1176902733-((3S,9aS)-8-(2-(2-aminopyrimidin-5-yl)-2,2-difluoroacetyl)octahydropyrazino[2,1-c][1,4]oxazin-3-yl)-6-fluoro-2-methylbenzonitrile

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 6228Dimethylformamide溶媒

実験手順

To a solution of 6-fluoro-2-methyl-3-((3S,9aS)-octahydropyrazino[2,1-c][1,4]oxazin-3-yl)benzonitrile (60 mg, 0.218 mmol) and 2-(2-aminopyrimidin-5-yl)-2,2-difluoroacetic acid (60.3 mg, 0.218 mmol) in anhydrous DMF (2724 μL) was added DIEA (133 μL, 0.763 mmol) followed by HATU (149 mg, 0.392 mmol). The mixture was stirred at RT overnight. The reaction mixture was diluted with methanol and purified on mass-directed preparative HPLC, Polar method (Column: Sunfire Prep C18, OBD 5 um, 30×100 mm). LC/MS: [(M+1)]+=447.08; 1H NMR (500 MHz, DMSO-d6) δ 8.36 (s, 2H), 8.11-8.17 (m, 1H), 7.30-7.39 (m, 3H), 4.83-4.92 (m, 1H), 4.07-4.27 (m, 1H), 3.43-3.76 (m, 2H), 3.00-3.37 (m, 4H), 2.72-2.96 (m, 2H), 2.58-2.68 (m, 1H), 2.16-2.55 (m, 4H).

後処理

  1. custompurified on mass-directed preparative HPLC, Polar method (Column: Sunfire Prep C18, OBD 5 um, 30×100 mm)

出典と根拠

ORDレコード
ord-bdc746e352394ad590daf9b298982a93
出典データセット
uspto-grants-2015_12
特許番号
US09206199B2

反応ノート

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