一水碳酸钠 → HCID 178476554，化合物

HRID 51591

反应方程式

HRID 51591 反应方程式
Cl.I[C:3]1[C:11]2[C:10]([NH2:12])=[N:9][CH:8]=[N:7][C:6]=2[N:5]([C@H:13]2[CH2:18][CH2:17][C@H:16]([N:19]3[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]3)[CH2:15][CH2:14]2)[CH:4]=1.[O:26]([C:33]1[CH:40]=[CH:39][C:38](B2[O:45][C:44]([CH3:47])(C)C(C)(C)O2)=[CH:37][C:34]=1[CH:35]=[O:36])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.[OH2:50].C(=O)([O-])[O-:52].[Na+].[Na+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:44]([OH:52])(=[O:45])[CH3:47].[C:27]([OH:26])(=[O:50])[CH3:28].[NH2:12][C:10]1[C:11]2[C:3]([C:38]3[CH:39]=[CH:40][C:33]([O:26][C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)=[C:34]([CH:37]=3)[CH:35]=[O:36])=[CH:4][N:5]([C@H:13]3[CH2:18][CH2:17][C@H:16]([N:19]4[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]4)[CH2:15][CH2:14]3)[C:6]=2[N:7]=[CH:8][N:9]=1

参与物

7

反应物 3

HCID 2735133一水碳酸钠HCID 112442242-Phenoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzaldehydeHCID 178480949HCID 178480949，化合物

产物 1

HCID 178476554HCID 178476554，化合物收率 102.9%

试剂、催化剂与溶剂 3

HCID 178418397HCID 178418397，化合物催化剂HCID 962聚[6-[4-(4-氰基苯基)苯氧基]己基甲基丙烯酸酯]溶剂HCID 8071乙二醇二甲醚溶剂

反应条件

温度
85 °C

实验过程

A mixture of trans-5-iodo-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride (750 mg, 1.63 mmol), 2-phenoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzaldehyde (635 mg, 1.96 mmol), sodium carbonate monohydrate (490 mg, 3.92 mmol) and tetrakis(triphenylphosphine)palladium(0) (115 mg, 0.1 mmol) in ethylene glycol dimethyl ether (40 mL) and water (20 mL) was heated at 85° C. for 18 hours. The mixture was cooled, concentrated under reduced pressure then purified by preparative RP-HPLC then lyophilized to give trans-5-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-phenoxybenzaldehyde bisacetate (636 mg, 68%). A portion of this compound (75 mg, 0.132 mmol) was dissolved in ethanol (2 mL) and the treated with maleic acid (61 mg, 0.526 mmol) in ethanol (1 mL). The precipitate was collected by filtration and dried under reduced pressure: 1H NMR (DMSO-d6, 400 MHz) δ 10.41(s, 1H), 8.22(s, 1H), 7.88(s, 1H), 7.72(d, 1H), 7.60(s, 1H), 7.47(t, 2H), 7.24(m, 3H), 7.08(d, 1H), 6.62 (bs, 2H), 6.16(s, 6H), 4.61(m, 1H), 2.5-3.4(m, 9H), 2.69(s, 3H), 1.8-2.1 (m, 6H), 1.56 (m, 2H); MS MH+511.4; RP-HPLC (Hypersil HS, 5 μm, 100 A 4.6×250 mm; 5%-100% acetonitrile—0.05 M ammonium acetate over 25 min, 1 ml/min) tr 14.55 min.

后处理

  1. temperatureThe mixture was cooled
  2. concentrationconcentrated under reduced pressure
  3. customthen purified by preparative RP-HPLC

来源与证据

ORD记录
ord-13f9f053a72b4df1b254015f5422fb99
来源数据集
uspto-grants-2004_03
专利号
US06713474B2

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