Sodium Carbonate → HCID 178489733, compound

HRID 656601Notes

Reaction equation

HRID 656601 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([CH2:7][CH2:8][O:9]/[N:10]=[C:11]2\[NH:12][C@@H:13]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=3Br)[CH2:14][C:15]3[N:16]=[C:17]([NH2:22])[N:18]=[C:19]([CH3:21])[C:20]\2=3)[CH2:3][CH2:2]1.B1([C:45]2[CH:50]=[CH:49][CH:48]=[C:47]([O:51][CH3:52])[N:46]=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]>[O:1]1[CH2:6][CH2:5][N:4]([CH2:7][CH2:8][O:9]/[N:10]=[C:11]2\[NH:12][C@@H:13]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=3[C:45]3[CH:50]=[CH:49][CH:48]=[C:47]([O:51][CH3:52])[N:46]=3)[CH2:14][C:15]3[N:16]=[C:17]([NH2:22])[N:18]=[C:19]([CH3:21])[C:20]\2=3)[CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 162178652-(6-Methoxypyridin-2-yl)-6-phenyl-1,3,6,2-dioxazaborocaneHCID 178433354HCID 178433354, compound

Product 1

HCID 178489733HCID 178489733, compoundYield 61.9%

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 (R,Z)-2-amino-7-(2-bromo-4-fluorophenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one O-2-morpholinoethyl oxime (100 mg, 0.21 mmol) in DMA was added 6-methoxypyridine-2-boronic acid N-phenyldiethanolamine ester (250 mg, 0.84 mmol), Pd(dppf)2Cl2 (17 mg, 0.02 mmol), and 2N Na2CO3 (522 μL, 1.05 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 (R,Z)-2-amino-7-(4-fluoro-2-(6-methoxypyridin-2-yl)phenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one O-2-morpholinoethyl oxime (67.4 mg, 0.13 mmol). 1H NMR (400 MHz, CHLOROFORM-d) δ 2.81 (s, 3H), 2.95 (td, J=11.87, 3.79 Hz, 2H), 3.12 (dd, J=17.18, 9.60 Hz, 1H), 3.34-3.56 (m, 3H), 3.70 (dd, J=11.75, 3.41 Hz, 2H), 3.84-4.06 (m, 7H), 4.39 (t, J=4.80 Hz, 2H), 4.94 (dd, J=9.60, 4.04 Hz, 1H), 6.81 (d, J=8.34 Hz, 1H), 7.06 (d, J=7.07 Hz, 1H), 7.08-7.21 (m, 2H), 7.50 (dd, J=8.59, 5.31 Hz, 1H), 7.68-7.81 (m, 1H). [M+H] calc'd for C26H30FN7O3, 508. found, 508.

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-15f520e9714543089a8dbc6d625f5a98
Source dataset
uspto-grants-2011_12
Patent number
US08071766B2

Reaction notes

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