Acetic Acid → HCID 178442411, compound

HRID 1055077Notes

Reaction equation

HRID 1055077 reaction equation
[OH-].[Na+].[OH:3][NH:4][C:5](N)=[O:6].Br[CH:9]([CH:14](Br)[CH2:15][CH:16]([NH:21][C:22]1[C:27]([F:28])=[CH:26][N:25]=[C:24]([C:29]2[C:37]3[C:32](=[N:33][CH:34]=[C:35]([F:38])[CH:36]=3)[NH:31][CH:30]=2)[N:23]=1)[C:17]([CH3:20])([CH3:19])[CH3:18])C(OC)=O.CC(O)=O>O.CO>[F:28][C:27]1[C:22]([NH:21][CH:16]([C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:15][C:14]2[O:3][N:4]=[C:5]([OH:6])[CH:9]=2)=[N:23][C:24]([C:29]2[C:37]3[C:32](=[N:33][CH:34]=[C:35]([F:38])[CH:36]=3)[NH:31][CH:30]=2)=[N:25][CH:26]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 3657HydroxyureaHCID 14798Sodium HydroxideHCID 86714756methyl 2,3-dibromo-5-((5-fluoro-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)-6,6-dimethylheptanoate2×

Product 1

HCID 178442411HCID 178442411, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a solution of NaOH (0.015 g) dissolved in water (0.410 mL) was added hydroxyurea (0.008 g, 0.100 mmol). The resulting mixture was stirred for 30 minutes before the dropwise addition of methyl 2,3-dibromo-5-((5-fluoro-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)-6,6-dimethylheptanoate, 85a, (0.064 g, 0.110 mmol) in MeOH (0.150 mL). The solution was stirred for 6 hours before the addition of AcOH (0.031 mL). The residue was purified by reverse phase preparative HPLC to afford the desired product: 1H NMR (300 MHz, MeOD) δ 8.57 (dd, J=9.7, 2.8 Hz, 1H), 8.16 (d, J=5.5 Hz, 2H), 8.00 (d, J=4.1 Hz, 1H), 5.68 (s, 1H), 3.03 (ddd, J=27.4, 15.4, 12.3 Hz, 2H), 1.10 (d, J=3.3 Hz, 11H); LCMS Gradient 10-90%, 0.1% formic acid, 5 minutes, C18/ACN, RT=2.15 minutes (M+H) 416.04.

Workup

  1. customThe residue was purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-1c44517c02f44aa592d5f8ced502462f
Source dataset
uspto-grants-2016_07
Patent number
US09394302B2

Reaction notes

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