Cesium carbonate → HCID 178489726, compound

HRID 656610Notes

Reaction equation

HRID 656610 reaction equation
[NH2:1][C:2]1[N:3]=[C:4]([CH3:29])[C:5]2=[C:6]([CH2:8][C@H:9]([C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=3[C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([O:27][CH3:28])[N:22]=3)[NH:10]/[C:11]/2=[N:12]\[OH:13])[N:7]=1.C([O-])([O-])=O.[Cs+].[Cs+].I[CH2:37][CH2:38][C@H:39]1[CH2:43][O:42][C:41]([CH3:45])([CH3:44])[O:40]1>CN(C=O)C>[CH3:44][C:41]1([CH3:45])[O:40][C@@H:39]([CH2:38][CH2:37][O:13]/[N:12]=[C:11]2\[NH:10][C@@H:9]([C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=3[C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([O:27][CH3:28])[N:22]=3)[CH2:8][C:6]3[N:7]=[C:2]([NH2:1])[N:3]=[C:4]([CH3:29])[C:5]\2=3)[CH2:43][O:42]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 11076039(4S)-4-(2-iodoethyl)-2,2-dimethyl-1,3-dioxolaneHCID 178489739HCID 178489739, compound2×

Product 1

HCID 178489726HCID 178489726, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (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 oxime (86 g or Compound 61, 10.0 mg, 0.025 mmol) in dry DMF (1 mL) was added Cs2CO3 (12.2 mg, 0.0375 mmol) and the reaction mixture stirred at ambient temperature for 30 minutes. Then, (S)-4-(2-iodoethyl)-2,2-dimethyl-1,3-dioxolane (86d, 7.68 mg, 0.03 mmol) was added and the reaction mixture stirred overnight. LCMS showed complete consumption of starting material. The reaction mixture was poured onto crushed ice and the resulting solid was filtered, rinsed with cold water, and dried to afford (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-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)ethyl oxime (86 h, 8.2 mg, 63%) as a light brown solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.33 (s, 3H) 1.39 (s, 3H) 1.91-2.01 (m, 4H) 2.72 (s, 3H) 3.07 (dd, J=16.55, 10.48 Hz, 1H) 3.26 (dd, J=17.05, 4.93 Hz, 1H) 3.55 (dd, J=7.96, 7.20 Hz, 1H) 3.90 (s, 3H) 4.05 (dd, J=7.96, 5.94 Hz, 1H) 4.10-4.21 (m, 3H) 4.89 (dd, J=10.61, 3.79 Hz, 1H) 6.74 (d, J=8.84 Hz, 1H) 7.01 (d, J=8.08 Hz, 1H) 7.11-7.22 (m, 2H) 7.61-7.69 (m, 2H)MS (ES) [M+H] calculated for C27H32FN6O4, 523.24. found 523.50.

Workup

  1. stirringthe reaction mixture stirred overnight
  2. customconsumption of starting material
  3. additionThe reaction mixture was poured
  4. customonto crushed ice
  5. filtrationthe resulting solid was filtered
  6. washrinsed with cold water
  7. customdried

Sources & evidence

ORD record
ord-4ac8d1986b8046648b1f92dc7436f236
Source dataset
uspto-grants-2011_12
Patent number
US08071766B2

Reaction notes

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