4-Methylmorpholine → HCID 49842256, compound

HRID 1627150Notes

Reaction equation

HRID 1627150 reaction equation
[Cl:1][C:2]1[C:11]2[CH2:10][N:9]([C@H:12]([CH:16]([CH3:18])[CH3:17])[C:13](O)=[O:14])[C:8](=[O:19])[C:7]3=[CH:20][NH:21][C:5]([C:6]=23)=[N:4][CH:3]=1.[NH:22]1[CH2:25][CH:24]([C:26]#[N:27])[CH2:23]1.CN1CCOCC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C1COCC1>[Cl:1][C:2]1[C:11]2[CH2:10][N:9]([C@H:12]([CH:16]([CH3:18])[CH3:17])[C:13]([N:22]3[CH2:25][CH:24]([C:26]#[N:27])[CH2:23]3)=[O:14])[C:8](=[O:19])[C:7]3=[CH:20][NH:21][C:5]([C:6]=23)=[N:4][CH:3]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 221323843-AzetidinecarbonitrileHCID 67224695(R)-2-(6-chloro-3-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)-3-methylbutanoic acid

Product 1

HCID 49842256HCID 49842256, compoundYield 31.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To an 8 mL scintillation vial equipped for stirring was added (R)-2-(6-chloro-3-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)-3-methylbutanoic acid (10 mg, 0.032 mmol). THF (0.5 mL), azetidine-3-carbonitrile (2.7 mg, 0.032 mmol), 4-methylmorpholine (4.93 mg, 0.049 mmol) and HATU (14.83 mg, 0.039 mmol) were added and the solution was stirred at 25° C. for 1 h. The reaction mixture was purified via preparative mass trigger LC-MS (AcCN/H2O, 5-50%). The fractions were collected, concentrated, and dried in vacuo to afford the title compound as a semi-solid (3.7 mg, 30.6%). 1H NMR (400 MHz, CD3OD) δ 0.94 (t, J=6.32 Hz, 3 H) 1.07 (dd, J=18.19, 6.32 Hz, 3 H) 2.44-2.59 (m, 1 H) 3.47-3.79 (m, 1 H) 4.15-4.40 (m, 2 H) 4.57 (dt, J=9.73, 4.99 Hz, 1 H) 4.63-4.78 (m, 1 H) 4.84 (d, J=19.71 Hz, 1 H) 5.06-5.30 (m, 2 H) 7.82 (d, J=11.37 Hz, 1 H) 8.25 (d, J=5.56 Hz, 1 H). [M+H] calc'd for C18H18ClN5O2, 372; found, 372.4.

Workup

  1. customTo an 8 mL scintillation vial equipped
  2. stirringthe solution was stirred at 25° C. for 1 h
  3. customThe reaction mixture was purified via preparative mass trigger LC-MS (AcCN/H2O, 5-50%)
  4. customThe fractions were collected
  5. concentrationconcentrated
  6. customdried in vacuo

Sources & evidence

ORD record
ord-5561718297f94a4d9989562a93a6950e
Source dataset
uspto-grants-2014_07
Patent number
US08785429B2

Reaction notes

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