Nicotinic Acid → HCID 178493884, compound

HRID 339783Notes

Reaction equation

HRID 339783 reaction equation
[OH:1][C@H:2]([CH2:21][N:22]1[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1)[CH2:3][O:4][C:5]1[CH:6]=[CH:7][C:8]2[C:9]3[N:10]([CH2:18][CH2:19][N:20]=3)[C:11]([NH2:17])=[N:12][C:13]=2[C:14]=1[O:15][CH3:16].[C:28](O)(=[O:35])[C:29]1[CH:34]=[CH:33][CH:32]=[N:31][CH:30]=1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(CC1C=C(CN(C)C)C(O)=C(CN(C)C)C=1)C>[OH:1][C@H:2]([CH2:21][N:22]1[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1)[CH2:3][O:4][C:5]1[CH:6]=[CH:7][C:8]2[C:9]3[N:10]([CH2:18][CH2:19][N:20]=3)[C:11]([NH:17][C:28]([C:29]3[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=3)=[O:35])=[N:12][C:13]=2[C:14]=1[O:15][CH3:16]

Participants

6

Reactant 4

HCID 938Nicotinic AcidHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 178493885(2R)-1-[(5-amino-7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-8-yl)oxy]-3-piperidin-1-ylpropan-2-ol

Product 1

HCID 178493884HCID 178493884, compoundYield 67.6%

Reagents, catalysts & solvents 1

HCID 70262,4,6-Tris((dimethylamino)methyl)phenolSolvent

Procedure

To a slurry of N-(8-{[(2R)-2-hydroxy-3-(piperidin-1-yl)propyl]oxy}-7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)amine (0.125 g, 0.34 mmol) and nicotinic acid (0.052 g, 0.42 mmol, 1.3 equiv.) in DMF 3.6 mL) was added PyBOP (0.218 g, 0.42 mmol, 1.3 equiv.) followed by diisopropylethylamine (0.23 mL, 1.34 mmol, 4.0 equiv.). The resulting mixture was stirred at room temperature. After a few hours the mixture turned to a clear solution. The resulting solids were removed by filtration, washed sequentially with DMF, water, then MeOH, and dried at 50° C. under reduced pressure to afford N-(8-{[(2R)-2-hydroxy-3-(piperidin-1-yl)propyl]oxy}-7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)pyridine-3-carboxamide (0.11 g, 66%): HPLC ret. time 1.00 min.; 1H NMR (DMSO-d6+1 drop TFA-d) δ 1.30, 1.44 m, 1H), 1.58-1.71 (m, 2H), 1.72-1.85 (m, 3H), 2.89-3.56 (m, 2H), 3.18 (dd, J=10.1, 13.1 Hz, 1H), 3.25-3.31 (m, 1H), 3.45-3.52 (m, 2H), 4.03 (s, 3H), 4.20-4.29 (m, 4H), 4.38-4.49 (m, 1H), 4.53-4.60 (m, 2H), 7.48 (d, J=9.4 Hz, 1H), 7.85 (dd, J=5.3, 7.9 Hz, 1H), 8.04 (d, J=9.1 Hz, 1H), 8.82 (br d, J=8.1 Hz, 1H), 8.93 (dd, J=1.5, 5.3 Hz, 1H), 9.47 (d, J=1.5 Hz, 1H); mass spectrum m/z 479 ((M+1)+, 0.4%).

Workup

  1. waitAfter a few hours the mixture turned to a clear solution
  2. customThe resulting solids were removed by filtration
  3. washwashed sequentially with DMF, water
  4. dry with materialMeOH, and dried at 50° C. under reduced pressure

Sources & evidence

ORD record
ord-1d8e9aa45ce1419e92c735cdfa9269fd
Source dataset
uspto-grants-2014_11
Patent number
US08895549B2

Reaction notes

Loading…