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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 1014703
Notes
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Reaction equation

HRID 1014703 reaction equation
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]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 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

Product 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
Yield 31%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

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]+.

Workup

  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

Sources & evidence

ORD record
ord-decfbbfa3f0c4bbcb840d2b5f4f4c78d
Source dataset
uspto-grants-2011_07
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07981893B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes