Sodium Carbonate Monohydrate → HCID 178480937、化合物

HRID 51594

反応式

HRID 51594 の反応式
I[C:2]1[C:10]2[C:9]([NH2:11])=[N:8][CH:7]=[N:6][C:5]=2[N:4]([C@H:12]2[CH2:17][CH2:16][C@@H:15]([N:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)[CH2:14][CH2:13]2)[CH:3]=1.[F:25][C:26]1[CH:31]=[C:30](B2OC(C)(C)C(C)(C)O2)[CH:29]=[CH:28][C:27]=1[NH:41][C:42]1[O:43][C:44]2[CH:50]=[CH:49][CH:48]=[CH:47][C:45]=2[N:46]=1.O.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[NH2:11][C:9]1[C:10]2[C:2]([C:30]3[CH:29]=[CH:28][C:27]([NH:41][C:42]4[O:43][C:44]5[CH:50]=[CH:49][CH:48]=[CH:47][C:45]=5[N:46]=4)=[C:26]([F:25])[CH:31]=3)=[CH:3][N:4]([C@H:12]3[CH2:17][CH2:16][C@@H:15]([N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)[CH2:14][CH2:13]3)[C:5]=2[N:6]=[CH:7][N:8]=1

参加物

7

反応物 3

HCID 2735133Sodium Carbonate MonohydrateHCID 22347094N2-[2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1,3-benzoxazol-2-amineHCID 178480947HCID 178480947、化合物

生成物 1

HCID 178480937HCID 178480937、化合物収率 28%

試薬・触媒・溶媒 3

HCID 11979704Tetrakis(triphenylphosphine)palladium触媒HCID 962Water溶媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
80 °C

実験手順

To a solution of cis-5-iodo-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine (0.100 g, 0.227 mmol) in ethylene glycol dimethyl ether (3 mL) and water (1.5 mL) under nitrogen was added N2-[2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1,3-benzoxazol-2-amine (0.100 g, 0.283 mmol, 1.25 equiv.), tetrakis(triphenylphosphine) palladium (0) (0.013 mg, 0.011 mmol, 0.05 equiv), and sodium carbonate monohydrate (0.070 mg, 0.568 mmol, 2.5 equiv). The solution was stirred at 80° C. for 21 hours. The resulting yellow mixture was concentrated in vacuo to give a yellow oil. Purification by preparative HPLC (25 to 100% CH3CN in 0.1 N aqueous ammonium acetate over 20 minutes at 21 mL/min. using a 8μ Hypersil HS C18, 250×21 mm column, tr=6.4-8.5 min.) afforded cis-N2-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-1,3-benzoxazol-2-amine as a cream solid (34 mg, 28%). RP-HPLC (25 to 100% CH3CN in 0.1 N aqueous ammonium acetate over 10 min at 1 mL/min using a Hypersil HS C18, 250×4.6 mm column) tr=7.167 min., 98%; and m/z 540.8(MH+).

後処理

  1. concentrationThe resulting yellow mixture was concentrated in vacuo
  2. customto give a yellow oil
  3. customPurification by preparative HPLC (25 to 100% CH3CN in 0.1 N aqueous ammonium acetate over 20 minutes at 21 mL/min.
  4. customa 8μ Hypersil HS C18, 250×21 mm column, tr=6.4-8.5 min.

出典と根拠

ORDレコード
ord-fcff8d4ace9b4876980e29239982cb62
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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