Water → 4-Fluoro-2-(1-methyl-5-(5-(oxetan-3-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)-6-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)benzyl Acetate

HRID 1918882Notes

Reaction equation

[CH3:1][N:2]1[C:7](=[O:8])[C:6]([NH:9][C:10]2[CH:22]=[C:13]3[CH2:14][N:15]([CH:18]4[CH2:21][O:20][CH2:19]4)[CH2:16][CH2:17][N:12]3[N:11]=2)=[CH:5][C:4](B(O)O)=[CH:3]1.[C:26]([O:29][CH2:30][C:31]1[C:36]([N:37]2[CH2:49][CH2:48][N:40]3[C:41]4[CH2:42][CH2:43][CH2:44][CH2:45][C:46]=4[CH:47]=[C:39]3[C:38]2=[O:50])=[CH:35][C:34]([F:51])=[CH:33][C:32]=1Br)(=[O:28])[CH3:27].C([O-])([O-])=O.[Na+].[Na+].O>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:26]([O:29][CH2:30][C:31]1[C:36]([N:37]2[CH2:49][CH2:48][N:40]3[C:41]4[CH2:42][CH2:43][CH2:44][CH2:45][C:46]=4[CH:47]=[C:39]3[C:38]2=[O:50])=[CH:35][C:34]([F:51])=[CH:33][C:32]=1[C:4]1[CH:5]=[C:6]([NH:9][C:10]2[CH:22]=[C:13]3[CH2:14][N:15]([CH:18]4[CH2:21][O:20][CH2:19]4)[CH2:16][CH2:17][N:12]3[N:11]=2)[C:7](=[O:8])[N:2]([CH3:1])[CH:3]=1)(=[O:28])[CH3:27]

Participants

Conditions

Temperature: 130 °C

Procedure

A 25 mL vial was charged with 143a (238 mg, 0.7 mmol), 2-bromo-4-fluoro-6-(1-oxo-3,4,6,7,8,9-hexahydro-pyrazino[1,2-a]indol-2(1H)-yl)benzyl acetate 197d (300 mg, 0.7 mmol), Na2CO3 (147 mg, 1.4 mmol), PdCl2(dppf) (56 mg, 0.07 mmol) suspended in DME (15 mL), and H2O (1 mL). The resulting orange mixture was heated for 30 minutes in a Biotage microwave reactor at 130° C. After reaction the residue was purified by reverse phase Combi-flash eluting with 0.3% NH4HCO3 in 1:7 water/CH3CN to give 143b as a brown solid (150 mg, 33%). MS: (M+H)+ 656.

Workup

customAfter reaction the residue
customwas purified by reverse phase Combi-flash
washeluting with 0.3% NH4HCO3 in 1:7 water/CH3CN

Sources & evidence

ORD record: ord-dc21e519f7824f15b462115355f90e23
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08618107B2

Reaction notes

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