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Potassium Phosphate, Tribasic → (4-(1-Methyl-5-(5-(1-methylazetidin-3-yloxy)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridin-3-yl)methyl Acetate

HRID 1411811
Notes
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Reaction equation

HRID 1411811 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH:18]3[CH2:21][N:20]([CH3:22])[CH2:19]3)=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[C:23]([O:26][CH2:27][C:28]1[C:29]([N:43]2[CH2:55][CH2:54][N:46]3[C:47]4[CH2:48][CH2:49][CH2:50][CH2:51][C:52]=4[CH:53]=[C:45]3[C:44]2=[O:56])=[N:30][CH:31]=[CH:32][C:33]=1B1OC(C)(C)C(C)(C)O1)(=[O:25])[CH3:24].[O-]P([O-])([O-])=O.[K+].[K+].[K+].O.O.O.C([O-])(=O)C.[Na+]>C(#N)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]>[C:23]([O:26][CH2:27][C:28]1[C:29]([N:43]2[CH2:55][CH2:54][N:46]3[C:47]4[CH2:48][CH2:49][CH2:50][CH2:51][C:52]=4[CH:53]=[C:45]3[C:44]2=[O:56])=[N:30][CH:31]=[CH:32][C:33]=1[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH:18]3[CH2:21][N:20]([CH3:22])[CH2:19]3)=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1)(=[O:25])[CH3:24]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 23665404Sodium Acetate TrihydrateHCID 580442285-Bromo-1-methyl-3-(5-(1-methylazetidin-3-yloxy)pyridin-2-ylamino)pyridin-2(1H)-oneHCID 86684143(2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)methyl acetate

Product 1

HCID 86684387
(4-(1-Methyl-5-(5-(1-methylazetidin-3-yloxy)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridin-3-yl)methyl Acetate
Yield 52%

Reagents, catalysts & solvents 3

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
100 °C

Procedure

A 100-mL round-bottomed flask equipped with a reflux condenser was charged with 206f (108 mg, 0.30 mmol), 3-(acetoxymethyl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridin-4-ylboronic acid 113i (115 mg, 0.30 mmol), Pd(dppf)Cl2 (15 mg, 0.015 mmol), K3PO4 (135 mg, 0.60 mmol), sodium acetate trihydrate (90 mg, 0.60 mmol) in acetonitrile (10 mL) and water (0.5 mL). The system was evacuated and refilled with N2. The reaction mixture was heated at 100° C. for 2 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 25:1 dichloromethane/methanol to afford 206g (90 mg, 52%) as a yellow brown solid. MS-ESI: [M+H]+ 624.2.

Workup

  1. customA 100-mL round-bottomed flask equipped with a reflux condenser
  2. customThe system was evacuated
  3. additionrefilled with N2
  4. temperatureIt was then cooled to room temperature
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customthe resulting residue was purified by silica-gel column chromatography
  8. washeluting with 25:1 dichloromethane/methanol

Sources & evidence

ORD record
ord-dca57ff589f440d789566b251ef414fb
Source dataset
uspto-grants-2014_12
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08921353B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes