聚[6-[4-(4-氰基苯基)苯氧基]己基甲基丙烯酸酯] → tert-butyl (1-{5-chloro-2-[(1-methyl-1H-pyrazol-4-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}piperidin-3-yl)carbamate

HRID 577703笔记

反应方程式

HRID 577703 反应方程式
Cl[C:2]1[C:3]2[C:17]([Cl:18])=[CH:16][NH:15][C:4]=2[N:5]=[C:6]([NH:8][C:9]2[CH:10]=[N:11][N:12]([CH3:14])[CH:13]=2)[N:7]=1.[NH:19]1[CH2:24][CH2:23][CH2:22][C@@H:21]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])[CH2:20]1.CCN(C(C)C)C(C)C.O>CS(C)=O>[Cl:18][C:17]1[C:3]2[C:2]([N:19]3[CH2:24][CH2:23][CH2:22][CH:21]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:30])([CH3:29])[CH3:31])[CH2:20]3)=[N:7][C:6]([NH:8][C:9]3[CH:10]=[N:11][N:12]([CH3:14])[CH:13]=3)=[N:5][C:4]=2[NH:15][CH:16]=1

参与物

6

反应物 4

HCID 962聚[6-[4-(4-氰基苯基)苯氧基]己基甲基丙烯酸酯]HCID 81531N,N-二异丙基乙胺HCID 1514172(R)-3-Boc-氨基哌啶HCID 866796474,5-dichloro-N-(1-methyl-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-2-amine

产物 1

HCID 86679648tert-butyl (1-{5-chloro-2-[(1-methyl-1H-pyrazol-4-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}piperidin-3-yl)carbamate收率 44%

试剂、催化剂与溶剂 1

HCID 679二甲基亚砜溶剂

实验过程

A solution of 4,5-dichloro-N-(1-methyl-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-2-amine (85 mg, 0.30 mmol), (R)-tert-butyl piperidin-3-ylcarbamate (90 mg, 0.45 mmol) and DIEA (75 μL, 0.45 mmol) in DMSO (0.60 mL) was heated to 120° C. in a microwave for 10 min. The reaction solution was poured into water and filtered. The filtrate was extracted with EtOAc and the organic layer was dried over MgSO4, filtered and concentrated in vacuo. The solids were combined and purified via flash chromatography eluting with a gradient of 1%-5% of (10% NH4OH in MeOH) in DCM to give the title compound (59 mg, 44% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.38 (br. s., 1H), 8.74 (s, 1H), 7.82 (s, 1H), 7.49 (s, 1H), 7.04 (d, J=2.69 Hz, 1H), 6.89 (d, J=7.83 Hz, 1H), 3.96-4.11 (m, 2H), 3.78 (s, 3H), 3.51 (br. s., 1H), 2.85 (t, J=11.25 Hz, 1H), 2.75 (t, J=11.13 Hz, 1H), 1.85-1.94 (m, 1H), 1.75-1.84 (m, 1H), 1.70 (t, J=12.10 Hz, 1H), 1.38 (s, 9H), 1.31 (br. s., 1H). m/z (APCI+) for C20H27ClN8O2 447.2 (M+H)+.

后处理

  1. filtrationfiltered
  2. extractionThe filtrate was extracted with EtOAc
  3. dry with materialthe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. custompurified via flash chromatography
  7. washeluting with a gradient of 1%-5% of (10% NH4OH in MeOH) in DCM

来源与证据

ORD记录
ord-5be913d99ae7404c95496b8506cb8f8e
来源数据集
uspto-grants-2015_05
专利号
US09040547B2

反应笔记

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