Dimethylamine → HCID 68994646, compound

HRID 402121Notes

Reaction equation

HRID 402121 reaction equation
C(O)(=O)/C=C/C(O)=O.[S:9]1[CH:13]=[CH:12][C:11]2[CH:14]=[C:15]([CH:18]3[C:27]4[C:22](=[CH:23][C:24]([C:28]5[N:33]=[N:32][C:31]([N:34]([CH3:36])[CH3:35])=[CH:30][CH:29]=5)=[CH:25][CH:26]=4)[CH2:21][N:20]([CH3:37])[CH2:19]3)[CH:16]=[CH:17][C:10]1=2.N(C)C.CN(C=O)C>ClCCl>[S:9]1[CH:13]=[CH:12][C:11]2[CH:14]=[C:15]([CH:18]3[C:27]4[C:22](=[CH:23][C:24]([C:28]5[N:33]=[N:32][C:31]([N:34]([CH3:36])[CH3:35])=[CH:30][CH:29]=5)=[CH:25][CH:26]=4)[CH2:21][N:20]([CH3:37])[CH2:19]3)[CH:16]=[CH:17][C:10]1=2

Participants

5

Reactant 3

HCID 674DimethylamineHCID 6228DimethylformamideHCID 131727466HCID 131727466, compound

Product 1

HCID 68994646HCID 68994646, compoundYield 98%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of the product obtained from Step A (200 mg, 0.51 mmol), Me2NH (40% aq solution, 4 mL, 35 mmol) and DMF (10 mL) was placed in a sealed tube. The tube was then heated at 110° C. for 14 h. After cooled to room temperature, the reaction was diluted with dichloromethane (50 mL) and washed with water, brine, dried and concentrated. The residue was purified by a medium pressure chromatography (eluent: MeOH/EtOAc 1:9) to give [6-(4-benzo[b]thiophen-5-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-yl]-dimethylamine (200 mg, 98%) as a yellow semi-solid. The compound was dissolved in methanol (2 mL), and to this solution was added fumaric acid (60 mg, 0.52 mmol). To this solution was added water (15 mL). The resulting suspension was lyophilized on a freeze dryer overnight to give (+)-[6-(4-benzo[b]thiophen-5-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-yl]-dimethylamine, fumarate salt (230 mg, 88%, 98.0% AUC HPLC) as an off-white solid: [α]25D+32.5° (c 0.08, methanol); mp 116-119° C.; 1H NMR (500 MHz, CD3OD) δ 7.92 (d, J=8.3 Hz, 1H), 7.87 (bs, 1H), 7.81 (d, J=10.0 Hz, 1H), 7.77 (bs, 1H), 7.75 (d, J=8.3 Hz, 1H), 7.61 (d, J=5.4, 1H), 7.35 (d, J=5.4 Hz, 1H), 7.22 (d, J=8.3 Hz, 1H), 7.19 (d, J=9.6 Hz, 1H), 7.04 (d, J=8.3 Hz, 1H), 6.71 (s, 4H), 4.73-4.67 (m, 1H), 4.60-4.49 (m, 2H), 3.81-3.77 (m, 1H), 3.50-3.43 (m, 1H), 3.21 (s, 6H), 2.99 (s, 3H); ESI-MS m/z 401 [M+H]+; Anal Calcd. For C22H24N4S.2.0C4H4O4.0.25H2O: C, 60.32; H, 5.14; N, 8.79. Found: C, 60.03; H, 4.94; N, 8.87.

Workup

  1. customwas placed in a sealed tube
  2. temperatureAfter cooled to room temperature
  3. washwashed with water, brine
  4. customdried
  5. concentrationconcentrated
  6. customThe residue was purified by a medium pressure chromatography (eluent: MeOH/EtOAc 1:9)

Sources & evidence

ORD record
ord-3327137b43b643f086ca939abdb83d3e
Source dataset
uspto-grants-2014_06
Patent number
US08741901B2

Reaction notes

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