Sodium Carbonate → [4-Fluoro-2-(1-methyl-6-oxo-5-{4H,6H,7H-pyrazolo[3,2-c][1,4]oxazin-2-ylamino]pyridin-3-yl)-6-{6-oxo-8-thia-5-azatricyclo[7.4.0.02,7]trideca-1(9),2(7)-dien-5-yl}phenyl}methyl Acetate

HRID 1918890Notes

Reaction equation

HRID 1918890 reaction equation
[N:1]1[N:9]2[C:4]([CH2:5][O:6][CH2:7][CH2:8]2)=[CH:3][C:2]=1[NH:10][C:11]1[C:12](=[O:27])[N:13]([CH3:26])[CH:14]=[C:15](B2OC(C)(C)C(C)(C)O2)[CH:16]=1.[C:28]([O:31][CH2:32][C:33]1[C:38]([N:39]2[C:51](=[O:52])[C:50]3[S:49][C:48]4[CH2:47][CH2:46][CH2:45][CH2:44][C:43]=4[C:42]=3[CH2:41][CH2:40]2)=[CH:37][C:36]([F:53])=[CH:35][C:34]=1Br)(=[O:30])[CH3:29].C([O-])([O-])=O.[Na+].[Na+]>COCCOC.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:28]([O:31][CH2:32][C:33]1[C:38]([N:39]2[C:51](=[O:52])[C:50]3[S:49][C:48]4[CH2:47][CH2:46][CH2:45][CH2:44][C:43]=4[C:42]=3[CH2:41][CH2:40]2)=[CH:37][C:36]([F:53])=[CH:35][C:34]=1[C:15]1[CH:16]=[C:11]([NH:10][C:2]2[CH:3]=[C:4]3[N:9]([N:1]=2)[CH2:8][CH2:7][O:6][CH2:5]3)[C:12](=[O:27])[N:13]([CH3:26])[CH:14]=1)(=[O:30])[CH3:29]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 580437562-Bromo-4-fluoro-6-(1-oxo-3,4,5,6,7,8-hexahydrobenzothieno[2,3-c]pyridin-2(1H)-yl)benzyl AcetateHCID 580440283-(6,7-Dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-ylamino)-1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one

Product 1

HCID 58044275[4-Fluoro-2-(1-methyl-6-oxo-5-{4H,6H,7H-pyrazolo[3,2-c][1,4]oxazin-2-ylamino]pyridin-3-yl)-6-{6-oxo-8-thia-5-azatricyclo[7.4.0.02,7]trideca-1(9),2(7)-dien-5-yl}phenyl}methyl AcetateYield 50%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 150a (260 mg, 0.70 mmol), (2-bromo-4-fluoro-6-{6-oxo-8-thia-5-azatricyclo[7.4.0.02,7]trideca-1(9),2(7)-dien-5-yl}phenyl)methyl acetate 218a (225 mg, 0.50 mmol), PdCl2(dppf) (55 mg, 0.075 mmol), 2 M Na2CO3 solution (1.5 mL) in DME (8 mL) was heated at 120° C. under microwave irradiation for 0.5 h. The solvent was evaporated in vacuo and the residue was purified on reverse phase Combi-flash to give 150b (154 mg, 50%). MS: [M+H]+ 618.

Workup

  1. customThe solvent was evaporated in vacuo
  2. customthe residue was purified on reverse phase Combi-flash

Sources & evidence

ORD record
ord-718169cb58684e11a284313eede62e59
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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