Sodium Carbonate Monohydrate → HCID 178476554、化合物

HRID 51591

反応式

HRID 51591 の反応式
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

参加物

7

反応物 3

HCID 2735133Sodium Carbonate MonohydrateHCID 112442242-Phenoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzaldehydeHCID 178480949HCID 178480949、化合物

生成物 1

HCID 178476554HCID 178476554、化合物収率 102.9%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
85 °C

実験手順

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.

後処理

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

出典と根拠

ORDレコード
ord-13f9f053a72b4df1b254015f5422fb99
出典データセット
uspto-grants-2004_03
特許番号
US06713474B2

関連ノート

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