Water → (2-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-4-(5-{[2-(2-hydroxypropan-2-yl)pyrimidin-4-yl]amino}-1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)pyridin-3-yl)methyl Acetate

HRID 593022Notes

Reaction equation

HRID 593022 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][N:14]=[C:13]([C:17]([OH:20])([CH3:19])[CH3:18])[N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[C:21]([O:24][CH2:25][C:26]1[C:27]([N:35]2[CH2:46][CH2:45][N:44]3[C:37](=[CH:38][C:39]4[CH2:40][C:41]([CH3:48])([CH3:47])[CH2:42][C:43]=43)[C:36]2=[O:49])=[N:28][CH:29]=[CH:30][C:31]=1B(O)O)(=[O:23])[CH3:22].[O-]P([O-])([O-])=O.[K+].[K+].[K+].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].O1CCCC1>[C:21]([O:24][CH2:25][C:26]1[C:27]([N:35]2[CH2:46][CH2:45][N:44]3[C:37](=[CH:38][C:39]4[CH2:40][C:41]([CH3:48])([CH3:47])[CH2:42][C:43]=43)[C:36]2=[O:49])=[N:28][CH:29]=[CH:30][C:31]=1[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][N:14]=[C:13]([C:17]([OH:20])([CH3:19])[CH3:18])[N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1)(=[O:23])[CH3:22]

Participants

7

Reactant 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 86684340[4-(Dihydroxyboranyl)-2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridin-3-yl]methyl acetateHCID 866845005-Bromo-3-(2-(2-hydroxypropan-2-yl)pyrimidin-4-ylamino)-1-methylpyridin-2(1H)-one

Product 1

HCID 86684501(2-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-4-(5-{[2-(2-hydroxypropan-2-yl)pyrimidin-4-yl]amino}-1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)pyridin-3-yl)methyl AcetateYield 65.4%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolvent

Procedure

A 50-mL round-bottomed flask equipped with a reflux condenser was charged with 264b (170 mg, 0.50 mmol), (3-(acetoxymethyl)-2-(7,7-dimethyl-1-oxo-3,4,7,8-tetrahydro-1H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2(6H)-yl)pyridin-4-yl)boronic acid 199e (200 mg, 0.50 mmol), Pd(dppf)Cl2 (40 mg, 0.050 mmol), K3PO4 (212 mg, 1.0 mmol), water (0.5 mL), and tetrahydrofuran (10 mL). After three cycles of vacuum/argon flush, the mixture was heated at reflux for 6 h. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica-gel column chromatography eluting with 40:1 dichloromethane/methanol to afford 264c as brown solid (200 mg, 54%). MS-ESI: [M+H]+ 612.3

Workup

  1. customA 50-mL round-bottomed flask equipped with a reflux condenser
  2. customAfter three cycles of vacuum/argon flush
  3. temperaturethe mixture was heated
  4. temperatureat reflux for 6 h
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customthe resulting residue was purified by silica-gel column chromatography
  8. washeluting with 40:1 dichloromethane/methanol

Sources & evidence

ORD record
ord-b80750b337aa4c2d89dadda09b4b0422
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

Loading…