Potassium Phosphate, Tribasic → 2-(5-(6,7-Dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)-6-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)benzyl Acetate

HRID 1918886Notes

Reaction equation

Cl[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:19]=[C:14]3[CH2:15][O:16][CH2:17][CH2:18][N:13]3[N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1.[C:20]([O:23][CH2:24][C:25]1[C:30](B2OC(C)(C)C(C)(C)O2)=[CH:29][CH:28]=[CH:27][C:26]=1[N:40]1[CH2:52][CH2:51][N:43]2[C:44]3[CH2:45][CH2:46][CH2:47][CH2:48][C:49]=3[CH:50]=[C:42]2[C:41]1=[O:53])(=[O:22])[CH3:21].[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC([O-])=O.[Na+]>CC#N.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:20]([O:23][CH2:24][C:25]1[C:26]([N:40]2[CH2:52][CH2:51][N:43]3[C:44]4[CH2:45][CH2:46][CH2:47][CH2:48][C:49]=4[CH:50]=[C:42]3[C:41]2=[O:53])=[CH:27][CH:28]=[CH:29][C:30]=1[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:19]=[C:14]3[CH2:15][O:16][CH2:17][CH2:18][N:13]3[N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1)(=[O:22])[CH3:21]

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of 6-chloro-4-(6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-ylamino)-2-methylpyridazin-3(2H)-one 147a (400 mg, 1.42 mmol), 2-(1-oxo-3,4,6,7,8,9-hexa-hydropyrazino[1,2-a]indol-2(1H)-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-benzyl acetate 114a (660 mg, 1.42 mmol), PdCl2(dppf) (155 mg, 0.21 mmol), K3PO4 (150 mg), and NaOAc (50 mg) in MeCN (20 mL) and H2O (4 mL) was heated at 110° C. in sealed tube for 2 h. The solvent was evaporated in vacuo and the residue was purified on reverse phase Combi-flash to give 147b (273 mg, 33%). MS: [M+H]+ 584.

Workup

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

Sources & evidence

ORD record: ord-15905f653964484f8d72f45926f7487f
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08618107B2

Reaction notes

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