Dimethylamine → HCID 178489724, compound

HRID 1917522Notes

Reaction equation

HRID 1917522 reaction equation
[NH2:1][C:2]1[N:3]=[C:4]([CH3:35])[C:5]2=[C:6]([CH2:8][C@H:9]([C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=3[C:27]3[CH:32]=[CH:31][CH:30]=[C:29]([O:33][CH3:34])[N:28]=3)[NH:10]/[C:11]/2=[N:12]\[O:13][CH2:14][CH2:15][CH2:16][C:17]([OH:19])=O)[N:7]=1.[CH3:36][N:37]1CCOC[CH2:38]1.ClC(OCC(C)C)=O.CNC.CO>C1COCC1>[NH2:1][C:2]1[N:3]=[C:4]([CH3:35])[C:5]2=[C:6]([CH2:8][C@H:9]([C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=3[C:27]3[CH:32]=[CH:31][CH:30]=[C:29]([O:33][CH3:34])[N:28]=3)[NH:10]/[C:11]/2=[N:12]\[O:13][CH2:14][CH2:15][CH2:16][C:17]([N:37]([CH3:38])[CH3:36])=[O:19])[N:7]=1

Participants

7

Reactant 5

HCID 674DimethylamineHCID 887MethanolHCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 178489725HCID 178489725, compound

Product 1

HCID 178489724HCID 178489724, compoundYield 23.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (R,Z)-4-(2-amino-7-(4-fluoro-2-(6-methoxypyridin-2-yl)phenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-ylideneaminooxy)butanoic acid (101a, 26 mg, 0.054 mmol) in anhydrous THF was chilled in an ice bath and N-methylmorpholine (9 μL, 0.081 mmol) and isobutyl chloroformate (7.7 μL, 0.060 mmol) were added sequentially. The mixture was stirred under an N2 atmosphere for 20 min. A 33 wt % solution of dimethylamine in methanol (54 μL, 0.11 mmol) was added to the reaction which was subsequently allowed to warm to room temperature with stirring overnight. The THF was removed in vacuo and the residue was partitioned between ethyl acetate and water. The organic phase was washed with H2O×2 and dried over anhydrous Na2SO4. The ethyl acetate was removed in vacuo and the residue was purified via preparative HPLC to yield (R,Z)-4-(2-amino-7-(4-fluoro-2-(6-methoxypyridin-2-yl)phenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-ylideneaminooxy)-N,N-dimethylbutanamide (98, 6.4 mg, 0.0126 mmol).

Workup

  1. stirringwith stirring overnight
  2. customThe THF was removed in vacuo
  3. customthe residue was partitioned between ethyl acetate and water
  4. washThe organic phase was washed with H2O×2
  5. dry with materialdried over anhydrous Na2SO4
  6. customThe ethyl acetate was removed in vacuo
  7. customthe residue was purified via preparative HPLC

Sources & evidence

ORD record
ord-4f744cb0766e4818b07d731793b4d68d
Source dataset
uspto-grants-2013_12
Patent number
US08618290B2

Reaction notes

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