Sodium Carbonate → HCID 178489727, compound

HRID 656605Notes

Reaction equation

HRID 656605 reaction equation
[NH2:1][C:2]1[N:3]=[C:4]([CH3:29])[C:5]2=[C:6]([CH2:8][C@H:9]([C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:22]=3Br)[NH:10]/[C:11]/2=[N:12]\[O:13][CH2:14][CH2:15][C@H:16]([OH:20])[C:17]([NH2:19])=[O:18])[N:7]=1.B1([C:44]2[CH:49]=[CH:48][CH:47]=[C:46]([O:50][CH3:51])[N:45]=2)OCCN(C2C=CC=CC=2)CCO1.C([O-])([O-])=O.[Na+].[Na+]>CC(N(C)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]>[NH2:1][C:2]1[N:3]=[C:4]([CH3:29])[C:5]2=[C:6]([CH2:8][C@H:9]([C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:22]=3[C:44]3[CH:49]=[CH:48][CH:47]=[C:46]([O:50][CH3:51])[N:45]=3)[NH:10]/[C:11]/2=[N:12]\[O:13][CH2:14][CH2:15][C@H:16]([OH:20])[C:17]([NH2:19])=[O:18])[N:7]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 162178652-(6-Methoxypyridin-2-yl)-6-phenyl-1,3,6,2-dioxazaborocaneHCID 178433347HCID 178433347, compound

Product 1

HCID 178489727HCID 178489727, compoundYield 22.7%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of (S)-4-((Z)—((R)-2-amino-7-(2-bromo-4-fluorophenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-ylidene)aminooxy)-2-hydroxybutanamide (51 mg, 0.11 mmol) in DMA was added 6-methoxypyridine-2-boronic acid N-phenyldiethanolamine ester (130 mg, 0.44 mmol), Pd(dppf)2Cl2 (9 mg, 0.011 mmol), and 2N Na2CO3 (273 μL, 0.55 mmol). The resultant mixture was degassed with N2 for 5 min then heated in a sealed tube at 85° C. for 14 h. The reaction was allowed to cool to r.t. and filtered through a pad of Celite topped with anhydrous Na2SO4, rinsing with EtOAc and CH3OH. The filtrate was concentrated to provide a brown residue which was purified by preparative HPLC eluting with TFA/ACN/H2O. The solvent was removed on a rotary evaporator and the sample was dried under high vacuum to yield (S)-4-((Z)—((R)-2-amino-7-(4-fluoro-2-(6-methoxypyridin-2-yl)phenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-ylidene)aminooxy)-2-hydroxybutanamide (12.6 mg, 0.025 mmol). 1H NMR (400 MHz, MeOD) δ 1.76-1.93 (m, 1H), 2.16-2.35 (m, 1H), 2.80 (s, 3H), 3.18 (dd, J=16.80, 9.22 Hz, 1H), 3.32-3.42 (m, 1H), 3.90 (s, 3H), 4.10 (dd, J=8.72, 3.16 Hz, 1H), 4.13-4.31 (m, 2H), 5.07 (dd, J=9.09, 4.04 Hz, 1H), 6.79 (d, J=8.08 Hz, 1H), 7.12 (d, J=7.33 Hz, 1H), 7.15-7.28 (m, 2H), 7.66 (dd, J=8.59, 5.56 Hz, 1H), 7.71-7.83 (m, 1H). [M+H] calc'd for C24H26FN7O4, 496. found, 496.

Workup

  1. customThe resultant mixture was degassed with N2 for 5 min
  2. temperatureto cool to r.t.
  3. filtrationfiltered through a pad of Celite
  4. washrinsing with EtOAc and CH3OH
  5. concentrationThe filtrate was concentrated
  6. customto provide a brown residue which
  7. customwas purified by preparative HPLC
  8. washeluting with TFA/ACN/H2O
  9. customThe solvent was removed on a rotary evaporator
  10. customthe sample was dried under high vacuum

Sources & evidence

ORD record
ord-a59ee96b24314b2db7714ea57d8dae7e
Source dataset
uspto-grants-2011_12
Patent number
US08071766B2

Reaction notes

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