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 1502178노트

반응식

HRID 1502178 반응식
[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

참가 물질

7

반응물 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

생성물 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

시약·촉매·용매 2

HCID 887Methanol용매HCID 6228Dimethylformamide용매

실험 절차

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).

후처리

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

출처 및 근거

ORD 기록
ord-bdc746e352394ad590daf9b298982a93
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09206199B2

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