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Hydrochloric Acid → 2-(3-{6-[2-(2,4-Dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-propionic acid

HRID 216178
ノート
印刷プレビュー

反応式

HRID 216178 の反応式
Cl[C:2]1[N:7]=[C:6]([O:8][CH3:9])[N:5]=[C:4]([NH:10][CH2:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=2[Cl:20])[CH:3]=1.[C:21]([CH:24]([C:26]1[CH:27]=[C:28](B(O)O)[CH:29]=[CH:30][CH:31]=1)[CH3:25])([OH:23])=[O:22].O.Cl>C(#N)C.C([O-])([O-])=O.[Na+].[Na+].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>[Cl:20][C:14]1[CH:15]=[C:16]([Cl:19])[CH:17]=[CH:18][C:13]=1[CH2:12][CH2:11][NH:10][C:4]1[N:5]=[C:6]([O:8][CH3:9])[N:7]=[C:2]([C:28]2[CH:27]=[C:26]([CH:24]([CH3:25])[C:21]([OH:23])=[O:22])[CH:31]=[CH:30][CH:29]=2)[CH:3]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

8

反応物 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 576360046-Chloro-N-[2-(2,4-dichlorophenyl)ethyl]-2-methoxy-4-pyrimidinamine2 回HCID 576360703-(1-Carboxy-ethyl)-phenyl boronic acid2 回

生成物 1

HCID 576360542-(3-{6-[2-(2,4-Dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-propionic acid

試薬・触媒・溶媒 3

HCID 178418397
HCID 178418397、化合物
触媒
HCID 6342Acetonitrile溶媒
HCID 10340Sodium Carbonate溶媒

反応条件

温度
130 °C

実験手順

A solution of (6-chloro-2-methoxy-pyrimidin-4-yl)-[2-(2,4-dichloro-phenyl)-ethyl]-amine [170 mg, 0.51 mmol, Intermediate (44)] and 3-(1-carboxy-ethyl)-phenyl boronic acid [119 mg, 0.61 mmol, Intermediate (70)] in acetonitrile (2.5 mL) and aqueous Na2CO3 solution (0.4 M, 2.5 mL) is degassed with nitrogen for 5 minutes before addition of tetrakis(triphenylphosphine)palladium (0) (29.5 mg, 5 mol %). The reaction vessel is sealed and heated under microwave to 130° C. for 30 minutes. To the reaction mixture is added 2 mL of water, the pH is adjusted to about 7 using 2 N aqueous hydrochloric acid and this mixture is extracted three times with EtOAc (30 mL). The combined extracts are washed with brine, dried over sodium sulfate and concentrated. The resulting oil is subjected to silica gel chromatography eluting with 0 to 7% MeOH in DCM to give 2-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-propionic acid as a solid, which is treated with 1M hydrogen chloride in ether affording 2-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-propionic acid hydrochloride [122 mg, 50%, Example 49(a)] as a solid. LC/MS: RT=2.47 minutes, MS: 446 (M+H). 1H NMR [300 MHz, (CD3)2SO]: □12.4 (1H, br s), 7.36-7.8 (7H, m), 6.6 (1H, s), 4 (3H, s), 3.78 (1H, q), 3.68 (2H, m), 3.02 (2H, m), 1.42 (3H, d). IC50=1 nM

後処理

  1. customThe reaction vessel is sealed
  2. extractionthis mixture is extracted three times with EtOAc (30 mL)
  3. washThe combined extracts are washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. washeluting with 0 to 7% MeOH in DCM

出典と根拠

ORDレコード
ord-fc8fd486d86c4f6a90f01d6f6292a81a
出典データセット
uspto-grants-2012_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08193183B2

反応ノート

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