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Water → 6-(4-(2-Hydroxypropan-2-YL)phenyl)-1-((tetrahydro-2H-pyran-4-YL)methyl)-1H-imidazo[4,5-B]pyrazin-2(3H)-one

HRID 388109
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HRID 388109 반응식
O=C1NC2=N[CH:7]=[C:8]([C:10]3[CH:19]=[CH:18][C:13](C(OC)=O)=[CH:12][CH:11]=3)N=C2N1CC1CCOCC1.Br[C:29]1[N:34]=[C:33]2[N:35]([CH2:39][CH:40]3[CH2:45][CH2:44][O:43][CH2:42][CH2:41]3)[C:36](=[O:38])[NH:37][C:32]2=[N:31][CH:30]=1.[CH3:46]OC(C1C=CC(B(O)O)=CC=1)=O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[OH2:67]>CN(C=O)C.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:67][C:8]([C:10]1[CH:11]=[CH:12][C:13]([C:29]2[N:34]=[C:33]3[N:35]([CH2:39][CH:40]4[CH2:45][CH2:44][O:43][CH2:42][CH2:41]4)[C:36](=[O:38])[NH:37][C:32]3=[N:31][CH:30]=2)=[CH:18][CH:19]=1)([CH3:7])[CH3:46]
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참가 물질

8

반응물 5

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 27343694-Methoxycarbonylphenylboronic acidHCID 66699894Methyl 4-(2-oxo-3-((tetrahydro-2H-pyran-4-yl)methyl)-2,3-dihydro-1H-imidazo[4,5-b]pyrazin-5-yl)benzoateHCID 866263956-Bromo-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one

생성물 1

HCID 24985540
6-(4-(2-Hydroxypropan-2-YL)phenyl)-1-((tetrahydro-2H-pyran-4-YL)methyl)-1H-imidazo[4,5-B]pyrazin-2(3H)-one
수율 31%

시약·촉매·용매 2

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

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온도
100 °C

실험 절차

Methyl 4-(2-oxo-3-((tetrahydro-2H-pyran-4-yl)methyl)-2,3-dihydro-1H-imidazo[4,5-b]pyrazin-5-yl)benzoate. 6-Bromo-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one (See Example 101.B) (500 mg, 1.59 mmol), 4-(methoxycarbonyl)phenylboronic acid (317 mg, 1.92 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane (130 mg, 0.16 mmol) and potassium phosphate (1.35 g, 6.36 mmol) in DMF (40 mL) and water (10 mL) were reacted according to General Procedure B. 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, and the residue was taken up in DMSO (2 mL) and heated at 100° C. until completely dissolved. Water was added upon cooling and the desired product precipitated out of solution. The precipitate was collected by vacuum filtration, washed with water and dried under high vacuum to provide the title compound (180 mg, 31% yield) as a colorless solid. MS (ESI) m/z 369.2 [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. dissolutionuntil completely dissolved
  4. additionWater was added
  5. temperatureupon cooling
  6. customthe desired product precipitated out of solution
  7. filtrationThe precipitate was collected by vacuum filtration
  8. washwashed with water
  9. customdried under high vacuum

출처 및 근거

ORD 기록
ord-eef959a5e17146d19647b12bb5d4fa17
출처 데이터셋
uspto-grants-2013_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08372976B2

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