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

HRID 216245

반응식

HRID 216245 반응식
Cl[C:2]1[CH:7]=[C:6]([NH:8][CH2:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=2[Cl:18])[N:5]=[C:4]([CH2:19][OH:20])[N:3]=1.[C:21]([C:24]([C:27]1[CH:28]=[C:29](B(O)O)[CH:30]=[CH:31][CH:32]=1)([CH3:26])[CH3:25])([OH:23])=[O:22].C([O-])([O-])=O.[Cs+].[Cs+].Cl>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>[Cl:18][C:12]1[CH:13]=[C:14]([Cl:17])[CH:15]=[CH:16][C:11]=1[CH2:10][CH2:9][NH:8][C:6]1[N:5]=[C:4]([CH2:19][OH:20])[N:3]=[C:2]([C:29]2[CH:28]=[C:27]([C:24]([CH3:26])([CH3:25])[C:21]([OH:23])=[O:22])[CH:32]=[CH:31][CH:30]=2)[CH:7]=1

참가 물질

8

반응물 4

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 442489972-(3-Boronophenyl)-2-methylpropanoic acidHCID 86240106{4-Chloro-6-[2-(2,4-dichloro-phenyl)-ethylamino]-pyrimidin-2-yl}-methanol

생성물 1

HCID 576360132-(3-{6-[2-(2,4-Dichloro-phenyl)-ethylamino]-2-hydroxymethyl-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid수율 18%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매2회HCID 80711,2-Dimethoxyethane용매

반응 조건

온도
90 °C

실험 절차

Argon is bubbled through a mixture of {4-chloro-6-[2-(2,4-dichloro-phenyl)-ethylamino]-pyrimidin-2-yl}-methanol (67 mg, 0.2 mmol), 3-(1-Carboxy-1-methyl-ethyl)-phenyl boronic acid [92 mg, 0.44 mmol, see Example 49(b) step 2], Cs2CO3 (197 mg, 0.6 mmol), and tetrakis(triphenylphosphine)palladium (0) (16.3 mg, 0.014 mmol) in ethylene glycol dimethyl ether (1.6 mL) and water (0.4 mL), for a period of 10 minutes. The reaction vessel is sealed and heated to 90° C. After stirring for 16 hours the mixture is diluted with water (25 mL, brought to pH 4 with HCl and extracted thrice with EtOAc (25 mL). The organic extracts are combined and dried over magnesium sulfate, filtered and concentrated to afford 2-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-hydroxymethyl-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid [16.5 mg, 18%, Example 86] as a solid. LCMS RT=2.47 minutes, MS: 460 (M+H). IC50=71 nM

후처리

  1. customThe reaction vessel is sealed
  2. extractionextracted thrice with EtOAc (25 mL)
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated

출처 및 근거

ORD 기록
ord-bfc8ad30498541a4b35fc3ef54383c35
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08193183B2

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