Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → tert-butyl 3-(5-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)piperidine-1-carboxylate

HRID 1968191Notes

Reaction equation

HRID 1968191 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([NH:14][CH2:15][C:16]2[C:24]3[C:23]([C:25]([OH:27])=O)=[CH:22][CH:21]=[N:20][C:19]=3[NH:18][CH:17]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CN(C1C=CN=CC=1)C>[O:27]=[C:25]1[C:23]2[CH:22]=[CH:21][N:20]=[C:19]3[NH:18][CH:17]=[C:16]([C:24]=23)[CH2:15][N:14]1[CH:10]1[CH2:11][CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:9]1

Participants

5

Reactant 2

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 672243403-((1-(tert-butoxycarbonyl)piperidin-3-ylamino)methyl)-1H-pyrrolo[2,3-b]pyridine-4-carboxylic acid

Product 1

HCID 49841899tert-butyl 3-(5-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

3-((1-(tert-butoxycarbonyl)piperidin-3-ylamino)methyl)-1H-pyrrolo[2,3-b]pyridine-4-carboxylic acid was dissolved in DMF (5 mL). HATU (914 mg, 2.4 mmol) and DMAP (196 mg, 1.6 mmol) were added, and the reaction stirred at rt for 2 h. The solution was concentrated in vacuo and purified by preparative HPLC eluting with a gradient of 30% to 50% Solvent B in Solvent A to give 123 mg of the title compound as a light yellow solid. 1H NMR (400 MHz, CD3OD) δ 1.48 (s, 9 H) 1.59-1.70 (m, 1 H) 1.88 (d, J=13.39 Hz, 1 H) 1.95-2.02 (m, 1 H) 2.06 (dd, J=12.25, 3.92 Hz, 1 H) 2.75 (br. s., 1 H) 3.15 (t, J=11.62 Hz, 1 H) 4.04-4.20 (m, 2 H) 4.51 (br. s., 1 H) 4.93-5.14 (m, 2 H) 7.44 (s, 1 H) 7.58 (d, J=5.31 Hz, 1 H) 8.43 (d, J=5.56 Hz, 1 H). [M+H] found 357.

Workup

  1. concentrationThe solution was concentrated in vacuo
  2. custompurified by preparative HPLC
  3. washeluting with a gradient of 30% to 50% Solvent B in Solvent A

Sources & evidence

ORD record
ord-8a6881d805a841e09911bf5400a9a25a
Source dataset
uspto-grants-2013_04
Patent number
US08420816B2

Reaction notes

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