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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
ノート
印刷プレビュー

反応式

HRID 1014703 の反応式
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]
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 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

生成物 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
収率 31%

試薬・触媒・溶媒 2

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

反応条件

温度
100 °C

実験手順

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]+.

後処理

  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

出典と根拠

ORDレコード
ord-decfbbfa3f0c4bbcb840d2b5f4f4c78d
出典データセット
uspto-grants-2011_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07981893B2

反応ノート

読み込み中…

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