Sodium Carbonate → (S)-2-((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)-4-hydroxy-N,N-dimethylbutanamide

HRID 656622Notes

Reaction equation

HRID 656622 reaction equation
[NH2:1][C:2]1[N:3]=[C:4]([CH3:31])[C:5]2=[C:6]([CH2:8][C@H:9]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=3Br)[NH:10]/[C:11]/2=[N:12]\[O:13][C@@H:14]([CH2:20][CH2:21][OH:22])[C:15]([N:17]([CH3:19])[CH3:18])=[O:16])[N:7]=1.[CH3:32][O:33][C:34]1[N:39]=[C:38](B2OCCN(C3C=CC=CC=3)CCO2)[CH:37]=[CH:36][CH:35]=1.C([O-])([O-])=O.[Na+].[Na+]>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].CC(N(C)C)=O>[NH2:1][C:2]1[N:3]=[C:4]([CH3:31])[C:5]2=[C:6]([CH2:8][C@H:9]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=3[C:38]3[CH:37]=[CH:36][CH:35]=[C:34]([O:33][CH3:32])[N:39]=3)[NH:10]/[C:11]/2=[N:12]\[O:13][C@@H:14]([CH2:20][CH2:21][OH:22])[C:15]([N:17]([CH3:19])[CH3:18])=[O:16])[N:7]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 162178652-(6-Methoxypyridin-2-yl)-6-phenyl-1,3,6,2-dioxazaborocaneHCID 178433355HCID 178433355, compound

Product 1

HCID 178489737(S)-2-((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)-4-hydroxy-N,N-dimethylbutanamideYield 37.8%

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 (S)-2-((Z)—((R)-2-amino-7-(2-bromo-4-fluorophenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-ylidene)aminooxy)-4-hydroxy-N,N-dimethylbutanamide (26 mg, 0.052 mmol), 2-(6-methoxypyridin-2-yl)-6-phenyl-1,3,6,2-dioxazaborocane (78 mg, 0.262 mmol), Pd(dppf)2Cl2 (7.68 mg, 0.01 mmol), 2N aq Na2CO3 (0.131 mL, 0.262 mmol) and DMA (2.0 mL) was degassed with N2 and heated at 85° C. for 4 h. Cooled to r.t., filtered trough celite and purified by prep LCMS to afford (S)-2-((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)-4-hydroxy-N,N-dimethylbutanamide (93, 10.3 mg, 37%) as off-white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ 2.04-2.15 (m, 2H) 2.60 (s, 3H) 2.97 (s, 3H) 3.01-3.07 (m, 1H) 3.13 (s, 3H) 3.30 (ddd, J=16.42, 3.79, 1.52 Hz, 1H) 3.70-3.84 (m, 2H) 3.89 (s, 3H) 4.90 (dd, J=10.74, 3.66 Hz, 1H) 5.12 (t, J=6.32 Hz, 1H) 5.26 (br. s., 1H) 5.78 (s, 1H) 6.74 (dd, J=8.34, 0.76 Hz, 1H) 7.02 (dd, J=7.20, 0.88 Hz, 1H) 7.11-7.21 (m, 2H) 7.65 (dd, J=8.34, 7.07 Hz, 2H). MS (ES) [M+H] calculated for C26H31FN7O4, 524.56. found 524.40.

Workup

  1. customwas degassed with N2
  2. temperatureCooled to r.t.
  3. filtrationfiltered trough celite
  4. custompurified by prep LCMS

Sources & evidence

ORD record
ord-77a1b796c0ca45de8a61c65dc9022d9d
Source dataset
uspto-grants-2011_12
Patent number
US08071766B2

Reaction notes

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