Triethylamine → Nvp-tnks-656

HRID 713476Notes

Reaction equation

HRID 713476 reaction equation
[CH:1]1([CH2:4][NH:5][CH2:6][C:7]2[NH:8][C:9](=[O:17])[C:10]3[CH2:16][O:15][CH2:14][CH2:13][C:11]=3[N:12]=2)[CH2:3][CH2:2]1.[CH3:18][O:19][C:20]1[CH:37]=[CH:36][C:23]([C:24]([CH:26]2[CH2:31][CH2:30][N:29]([CH2:32][C:33](O)=[O:34])[CH2:28][CH2:27]2)=[O:25])=[CH:22][CH:21]=1.C(N(CC)CC)C.O.N1(O)C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>ClCCl>[CH:1]1([CH2:4][N:5]([CH2:6][C:7]2[NH:8][C:9](=[O:17])[C:10]3[CH2:16][O:15][CH2:14][CH2:13][C:11]=3[N:12]=2)[C:33](=[O:34])[CH2:32][N:29]2[CH2:30][CH2:31][CH:26]([C:24](=[O:25])[C:23]3[CH:22]=[CH:21][C:20]([O:19][CH3:18])=[CH:37][CH:36]=3)[CH2:27][CH2:28]2)[CH2:3][CH2:2]1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 712267662-(4-(4-Methoxybenzoyl)piperidin-1-YL)acetic acidHCID 1362440742-[(Cyclopropylmethyl-amino)-methyl]-3,5,7,8-tetrahydro-pyrano[4,3-d]pyrimidin-4-one

Product 1

HCID 136237316Nvp-tnks-656Yield 77.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a well stirred suspension of 2-[(Cyclopropylmethyl-amino)-methyl]-3,5,7,8-tetrahydro-pyrano[4,3-d]pyrimidin-4-one (15.66 g, 57.6 mmol) in dichloromethane (600 mL) was added 2-(4-(4-methoxybenzoyl)piperidin-1-yl)acetic acid (16.45 g, 59.3 mmol), followed by triethylamine (24 mL, 173 mmol), 1H-benzo[d][1,2,3]triazol-1-ol hydrate (21.41 g, 140 mmol) and N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (13.26 g, 69.2 mmol). The resulting yellow suspension was stirred for 12 h, filtered and then washed with water three times (250 mL, 150 mL, then 50 mL). The organic layer was washed twice with brine (50 mL), dried with Na2SO4, filtered and concentrated in vacuo (33.34 g). The residue was dissolved in 750 mL dichloromethane, and washed with a pH 9 KHCO3/K2CO3 solution (2×100 mL). The organic layer was washed twice with brine (50 mL), dried with Na2SO4, filtered and concentrated in vacuo (23.4 g). The crude material was dissolved in approximately 25 mL MeOH resulting in an orange solution and placed in a freezer overnight to form a slurry. The mixture was filtered, washed with MeOH and dried in vacuo to yield 21.959 g of the title compound as a white solid. HRMS calculated for C27H34N4O5 495.2607. found (ESI, [M+H]+), 495.2607, retention time=3.717 min. CHN analysis: calculated (results). C, 65.57 (65.17), H, 6.93 (6.64), N, 11.33 (11.39).

Workup

  1. stirringThe resulting yellow suspension was stirred for 12 h
  2. filtrationfiltered
  3. washwashed with water three times (250 mL, 150 mL
  4. washThe organic layer was washed twice with brine (50 mL)
  5. dry with materialdried with Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo (33.34 g)
  8. dissolutionThe residue was dissolved in 750 mL dichloromethane
  9. washwashed with a pH 9 KHCO3/K2CO3 solution (2×100 mL)
  10. washThe organic layer was washed twice with brine (50 mL)
  11. dry with materialdried with Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo (23.4 g)
  14. dissolutionThe crude material was dissolved in approximately 25 mL MeOH resulting in an orange solution
  15. customto form a slurry
  16. filtrationThe mixture was filtered
  17. washwashed with MeOH
  18. customdried in vacuo

Sources & evidence

ORD record
ord-ac94fbb259c947319dbdfa2d06144264
Source dataset
uspto-grants-2015_11
Patent number
US09181266B2

Reaction notes

Loading…