Sodium Carbonate → HCID 178489736, compound

HRID 1917525Notes

Reaction equation

HRID 1917525 reaction equation
[NH2:1][C:2]1[N:3]=[C:4]([CH3:27])[C:5]2=[C:6]([CH2:8][C@H:9]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3Br)[NH:10]/[C:11]/2=[N:12]\[O:13][CH2:14][C:15]([O:17]C)=[O:16])[N:7]=1.[CH3:28][O:29][C:30]1[N:35]=[C:34](B2OCCN(C3C=CC=CC=3)CCO2)[CH:33]=[CH:32][CH:31]=1.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]([CH3:27])[C:5]2=[C:6]([CH2:8][C@H:9]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[C:34]3[CH:33]=[CH:32][CH:31]=[C:30]([O:29][CH3:28])[N:35]=3)[NH:10]/[C:11]/2=[N:12]\[O:13][CH2:14][C:15]([OH:17])=[O:16])[N:7]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 162178652-(6-Methoxypyridin-2-yl)-6-phenyl-1,3,6,2-dioxazaborocaneHCID 178501863(R,Z)-methyl 2-(2-amino-7-(2-bromo-4-fluorophenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-ylideneaminooxy)acetate

Product 1

HCID 178489736HCID 178489736, compoundYield 31%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
85 °C

Procedure

A mixture of (R,Z)-methyl 2-(2-amino-7-(2-bromo-4-fluorophenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-ylideneaminooxy)acetate (105c, 175 mg, 0.4 mmol), 2-(6-methoxypyridin-2-yl)-6-phenyl-1,3,6,2-dioxazaborocane (298 mg, 1.0 mmol), Pd(dppf)2Cl2 (32.5 mg, 0.04 mmol), 2N Na2CO3 (1.0 mL, 2.0 mmol) in DMA (3 mL) was degassed with N2 and heated at 85° C. for over night. The reaction mixture was cooled to ambient temperature, diluted with ethyl acetate and filtered through celite. The filtrate was concentrated to afford brown oil which was purified by preparative LCMS to afford (R,Z)-2-(2-amino-7-(4-fluoro-2-(6-methoxypyridin-2-yl)phenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-ylideneaminooxy)acetic acid (105d, 56 mg, 31%) as white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.79 (s, 3H) 3.16 (dd, J=17.05, 10.48 Hz, 1H) 3.45 (dd, J=17.05, 3.92 Hz, 1H) 3.88 (s, 3H) 4.59 (d, J=3.03 Hz, 2H) 4.96 (dd, J=10.36, 3.79 Hz, 1H) 5.90 (brs, 1H) 6.76 (d, J=8.34 Hz, 1H) 7.02 (d, J=6.82 Hz, 1H) 7.14 (dd, J=9.09, 2.78 Hz, 1H) 7.19 (td, J=8.34, 2.78 Hz, 1H) 7.62 (dd, J=8.59, 5.56 Hz, 1H) 7.68 (dd, J=8.34, 7.33 Hz, 1H). MS (ES) [M+H] calculated for C22H22FN6O4, 453.16; found 453.30.

Workup

  1. customwas degassed with N2
  2. temperatureThe reaction mixture was cooled to ambient temperature
  3. additiondiluted with ethyl acetate
  4. filtrationfiltered through celite
  5. concentrationThe filtrate was concentrated
  6. customto afford brown oil which
  7. customwas purified by preparative LCMS

Sources & evidence

ORD record
ord-e3f619d586b042e480be566c30d5bc60
Source dataset
uspto-grants-2013_12
Patent number
US08618290B2

Reaction notes

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