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Potassium Phosphate, Tribasic → 6-(4-Hydroxyphenyl)-1-(2-morpholinoethyl)-1H-imidazo[4,5-B]pyrazin-2(3H)-one

HRID 388113
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HRID 388113 반응식
Cl.[OH:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:14]=[C:13]3[N:15]([CH2:19][CH2:20][N:21]4[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)[C:16](=[O:18])[NH:17][C:12]3=[N:11][CH:10]=2)=[CH:5][CH:4]=1.BrC1N=C2N(CCN3CCOCC3)C(=O)NC2=NC=1.CNC(C1C=CC(B(O)O)=CC=1)=O.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[OH:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]2[N:14]=[C:13]3[N:15]([CH2:19][CH2:20][N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)[C:16](=[O:18])[NH:17][C:12]3=[N:11][CH:10]=2)=[CH:7][CH:8]=1
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

8

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 27735264-(Methylcarbamoyl)benzeneboronic acidHCID 866263996-Bromo-1-(2-morpholinoethyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-oneHCID 1358710156-(4-Hydroxyphenyl)-1-(2-morpholinoethyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one hydrochloride

생성물 1

HCID 1358710166-(4-Hydroxyphenyl)-1-(2-morpholinoethyl)-1H-imidazo[4,5-B]pyrazin-2(3H)-one
수율 16%

시약·촉매·용매 3

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

6-(4-Hydroxyphenyl)-1-(2-morpholinoethyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one hydrochloride. 6-Bromo-1-(2-morpholinoethyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one (300 mg, 0.95 mmol), [4-(N-methylaminocarbonyl)phenyl]boronic acid (205 mg, 1.15 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane (80 mg, 0.09 mmol) and potassium phosphate (805 mg, 3.8 mmol) in DMF (30 mL) and water (8 mL) were reacted according to General Procedure C. The product was purified by reverse-phase semi-preparatory HPLC (30-100% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min). The desired fractions were concentrated, treated with 4N hydrochloric acid in diethylether (few drops) and sonicated. This procedure was repeated twice more to provide 6-(4-hydroxyphenyl)-1-(2-morpholinoethyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one (67 mg, 16%) as a colorless solid hydrochloride salt. 1H NMR (400 MHz, CD3OD-d6) δ 8.38 (s, 1H), 8.84 (d, J=8.4, 2H), 7.44 (s, 1H), 7.39 (d, J=8.4, 2H), 4.45 (t, J=5.6, 2H); 4.07 (d, J=12.4, 2H), 3.82 (d, J=12.4, 2H), 3.69-3.64 (m, 4H); MS (ESI) m/z 342.15 [M+1]+.

후처리

  1. customThe product was purified by reverse-phase semi-preparatory HPLC (30-100% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min)
  2. concentrationThe desired fractions were concentrated
  3. additiontreated with 4N hydrochloric acid in diethylether (few drops)
  4. customsonicated

출처 및 근거

ORD 기록
ord-d9989113d74b4b4e889544bcbba84419
출처 데이터셋
uspto-grants-2013_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08372976B2

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