Morpholine → HCID 178489735, compound

HRID 1917526Notes

Reaction equation

HRID 1917526 reaction equation
[NH2:1][C:2]1[N:3]=[C:4]([CH3:33])[C:5]2=[C:6]([CH2:8][C@H:9]([C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=3[C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([O:31][CH3:32])[N:26]=3)[NH:10]/[C:11]/2=[N:12]\[O:13][CH2:14][C:15](O)=[O:16])[N:7]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC.[NH:65]1[CH2:70][CH2:69][O:68][CH2:67][CH2:66]1>CN(C=O)C>[NH2:1][C:2]1[N:3]=[C:4]([CH3:33])[C:5]2=[C:6]([CH2:8][C@H:9]([C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=3[C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([O:31][CH3:32])[N:26]=3)[NH:10]/[C:11]/2=[N:12]\[O:13][CH2:14][C:15]([N:65]2[CH2:70][CH2:69][O:68][CH2:67][CH2:66]2)=[O:16])[N:7]=1

Participants

6

Reactant 4

HCID 8083MorpholineHCID 8471TriethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178489736HCID 178489736, compound

Product 1

HCID 178489735HCID 178489735, compoundYield 22%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (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, 0.05 mmol, 22.6 mg) in DMF (0.5 mL) was added HBTU (0.075 mmol, 28 mg), Et3N (0.125 mmol, 17 μL) and morpholine (0.1 mmol, 8.3 μL). The reaction mixture was stirred over night at r.t. and LCMS shows completion of the reaction. Purified by prep LCMS to afford the title compound (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)-1-morpholinoethanone (102, 5.7 mg, 22%) as off white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.83 (s, 3H) 3.15 (dd, J=17.31, 10.23 Hz, 2H) 3.43-3.51 (m, 2H) 3.63 (d, J=5.31 Hz, 2H) 3.65-3.71 (m, 4H) 3.89 (s, 3H) 4.71 (s, 2H) 4.97 (dd, J=10.36, 3.79 Hz, 1H) 5.96 (br. s., 1H) 6.77 (d, J=8.34 Hz, 1H) 7.03 (d, J=7.07 Hz, 1H) 7.14 (dd, J=9.35, 2.78 Hz, 1H) 7.19 (td, J=8.40, 2.65 Hz, 1H) 7.63 (dd, J=8.84, 5.56 Hz, 1H) 7.68 (dd, J=8.34, 7.33 Hz, 1H). MS (ES) [M+H] calculated for C26H28FN7O4, 522.22; found 522.00.

Workup

  1. customcompletion of the reaction
  2. customPurified by prep LCMS

Sources & evidence

ORD record
ord-bba475326c644cb292a8b8e61d40c37f
Source dataset
uspto-grants-2013_12
Patent number
US08618290B2

Reaction notes

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