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2-Cyano-4-methylpent-2-enoic acid → 2-[2-[[4-Amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]azetidine-1-carbonyl]-4-methyl-pent-2-enenitrile

HRID 1778436
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HRID 1778436 반응식
[C:1]([C:3](=[CH:7][CH:8]([CH3:10])[CH3:9])[C:4]([OH:6])=O)#[N:2].[NH:11]1[CH2:14][CH2:13][CH:12]1[CH2:15][N:16]1[C:20]2=[N:21][CH:22]=[N:23][C:24]([NH2:25])=[C:19]2[C:18]([C:26]2[CH:31]=[CH:30][C:29]([O:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)=[CH:28][C:27]=2[F:39])=[N:17]1.C1CN([P+](ON2N=NC3C=CC=NC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[NH2:25][C:24]1[N:23]=[CH:22][N:21]=[C:20]2[N:16]([CH2:15][CH:12]3[CH2:13][CH2:14][N:11]3[C:4]([C:3](=[CH:7][CH:8]([CH3:10])[CH3:9])[C:1]#[N:2])=[O:6])[N:17]=[C:18]([C:26]3[CH:31]=[CH:30][C:29]([O:32][C:33]4[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=4)=[CH:28][C:27]=3[F:39])[C:19]=12
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

5

반응물 3

HCID 2925472-Cyano-4-methylpent-2-enoic acidHCID 11038641((7-Azabenzotriazol-1-YL)oxy)tris(pyrrolidino)phosphonium hexafluorophosphateHCID 900012121-(Azetidin-2-ylmethyl)-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-amine

생성물 1

HCID 1240076262-[2-[[4-Amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]azetidine-1-carbonyl]-4-methyl-pent-2-enenitrile수율 39.8%

시약·촉매·용매

1
HCID 6344Dichloromethane용매

실험 절차

To a solution of 2-cyano-4-methyl-pent-2-enoic acid (30.7 mg, 0.220 mmol), 1-(azetidin-2-ylmethyl)-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-amine (57.5 mg, 0.150 mmol in DCM (2 mL) was added PyAOP (86.2 mg, 0.160 mmol) and TEA (0.06 mL, 0.440 mmol) and the resulting yellow solution stirred at rt for 1 h. LCMS showed that the reaction was complete and the crude mixture was directly loaded onto a silica gel cartridge for purification (3 to 5% MeOH: CH2Cl2). Removal of solvent from cleanest fractions afforded 30 mg of the desired compound 2-[2-[[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]azetidine-1-carbonyl]-4-methyl-pent-2-enenitrile (30 mg, 0.0586 mmol, 39.8% yield) as judged by LCMS. (M+1=512).

후처리

  1. customthe crude mixture was directly loaded onto a silica gel cartridge for purification (3 to 5% MeOH: CH2Cl2)
  2. customRemoval of solvent from cleanest fractions

출처 및 근거

ORD 기록
ord-ec27c3c6939a4a0bbe57bf509723e84f
출처 데이터셋
uspto-grants-2016_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09266895B2

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