Acetic Acid → HCID 24855227, compound

HRID 913083Notes

Reaction equation

Cl.Cl.[NH:3]1[CH2:8][CH2:7][CH:6]([NH:9][C:10]2[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][N:11]=2)[CH2:5][CH2:4]1.C(O)(=O)C.C(N(C(C)C)C(C)C)C.[CH2:31]([O:33][C:34]1[CH:35]=[C:36]([CH:39]=[CH:40][C:41]=1[CH3:42])[CH:37]=O)[CH3:32].C([BH3-])#N.[Na+]>C(O)C>[CH2:31]([O:33][C:34]1[CH:35]=[C:36]([CH:39]=[CH:40][C:41]=1[CH3:42])[CH2:37][N:3]1[CH2:4][CH2:5][CH:6]([NH:9][C:10]2[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][N:11]=2)[CH2:7][CH2:8]1)[CH3:32]

Participants

Conditions

Temperature: 55 °C

Procedure

To a solution of 6-(piperidin-4-ylamino)-nicotinonitrile dihydrochloride (41.3 mg, 0.15 mmol, 1.0 equiv; intermediate B2) in ethanol (2 mL), acetic acid (72.1 mg, 1.2 mmol, 8.0 equiv) and N-ethyl diisopropylamine (77.6 mg, 0.6 mmol, 4.0 equiv) was added 3-ethoxy-4-methyl-benzaldehyde (29.6 mg, 0.18 mmol, 1.2 equiv; intermediate E10, vide infra) and the mixture stirred at 55° C. After 1 h, sodium cyanoborohydride (47.1 mg, 0.75 mmol, 5.0 equiv), dissolved in ethanol (0.5 mL), was added and the mixture stirred at 55° C. over night. Removal of the solvent under reduced pressure and purification by preparative HPLC on reversed phase eluting with a gradient of acetonitrile/water provided 20.5 mg (39%) of the title compound. MS (ISP): 350.7 [M+H]+.

Workup

additionwas added
stirringthe mixture stirred at 55° C. over night
customRemoval of the solvent
customunder reduced pressure and purification by preparative HPLC on reversed phase
washeluting with a gradient of acetonitrile/water

Sources & evidence

ORD record: ord-dd5aa1d8387941e68ace338c7cab7e69
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08026255B2

Reaction notes

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