Triethylamine → HCID 58335816, compound

HRID 1890700Notes

Reaction equation

HRID 1890700 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:8]2[CH2:12][CH2:11][CH2:10][N:9]2[C:13]2[CH:14]=[CH:15][C:16]3[N:17]([C:19]([C:22]4[N:27]=[C:26]([C:28]5[CH:33]=[CH:32][N:31]=[C:30]([N:34]6[CH2:39][CH2:38][CH:37](O)[CH2:36][CH2:35]6)[CH:29]=5)[CH:25]=[CH:24][CH:23]=4)=[CH:20][N:21]=3)[N:18]=2)[CH:5]=[CH:6][CH:7]=1.C([N:43]([CH2:46][CH3:47])CC)C.[CH3:48]S(Cl)(=O)=O>C(Cl)Cl>[CH:46]1([NH:43][CH:37]2[CH2:38][CH2:39][N:34]([C:30]3[CH:29]=[C:28]([C:26]4[CH:25]=[CH:24][CH:23]=[C:22]([C:19]5[N:17]6[N:18]=[C:13]([N:9]7[CH2:10][CH2:11][CH2:12][CH:8]7[C:4]7[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=7)[CH:14]=[CH:15][C:16]6=[N:21][CH:20]=5)[N:27]=4)[CH:33]=[CH:32][N:31]=3)[CH2:35][CH2:36]2)[CH2:47][CH2:48]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 58335615HCID 58335615, compound

Product 1

HCID 58335816HCID 58335816, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

(N-cyclopropyl-1-(6-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2,4′-bipyridin-2′-yl)piperidin-4-amine) was prepared in the following manner. To a 20 mL reaction flask was added 1-(6-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2,4′-bipyridin-2′-yl)piperidin-4-ol (30 mg, 0.056 mmol) and 0.8 mL of methylene chloride. This solution was charged with triethylamine (0.10 mL, 0.69 mmol) and dropwise addition of methane sulfonyl chloride (MsCl, approx. 20 mg, 0.18 mmol). The resulting solution was stirred for 2 hours, followed by quenching with water, ethyl acetate extraction (3×30 mL), and the organic extracts were transferred to a 10 mL volume resealable vessel. The residue in the vessel was charged with 2 mL cyclopropylamine (excess, co-solvent) and 0.5 mL of THF. The vessel was sealed and heated for 6 hours at 90° C. Upon cooling, the contents of the vessel were concentrated to a volume of 1 mL and directly subjected to reverse phase separation (gradient, C-18 support, 10 to 70%, acetonitrile:water) to give (N-cyclopropyl-1-(6-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2,4′-bipyridin-2′-yl)piperidin-4-amine). 1H NMR (400 MHz, D3 acetonitrile) δ ppm 8.71 (br s, 1H), 8.41 (s, 1H) 8.26 (d, J=7.2 Hz, 1H), 7.99 (app d, J=6.7 Hz, 2H), 7.85 (d, J=6.2 Hz, 1H), 7.73 (br s, 1H), 7.63 (s, 1H), 7.42 (d, J=6.4 Hz, 1H), 7.39 (app q, J=6.8 Hz, 1H), 7.20 (d, J=7.2 Hz, 1H), 7.05 (dt, J=8.6, 1.9 Hz, 1H), 6.99-6.82 (m, 1H), 5.27 (d, J=6.4 Hz, 1H), 4.54 (app d, J=10 Hz, 2H), 4.00 (app q, J=3.9 Hz, 1H), 3.69-3.62 (m, 1H), 3.46 (app d, J=5.8 Hz, 1H), 2.98 (app q, J=4.2 Hz, 2H), 2.73 (br s, 2H), 2.47-2.35 (m, 1H), 2.13 (app dd, J=5.6 Hz, 2H), 2.08-2.03 (m, 2H), 1.89-1.86 (m, 1H), 0.82-0.66 (m, 5H). LRMS observed m/z 575.3 major ion (calcd for M+H, 575.3).

Workup

  1. custom(N-cyclopropyl-1-(6-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2,4′-bipyridin-2′-yl)piperidin-4-amine) was prepared in the following manner
  2. customTo a 20 mL reaction flask
  3. customby quenching with water, ethyl acetate extraction (3×30 mL)
  4. customthe organic extracts were transferred to a 10 mL volume resealable vessel
  5. additionThe residue in the vessel was charged with 2 mL cyclopropylamine (excess, co-solvent) and 0.5 mL of THF
  6. customThe vessel was sealed
  7. temperatureUpon cooling
  8. concentrationthe contents of the vessel were concentrated to a volume of 1 mL
  9. customphase separation (gradient, C-18 support, 10 to 70%, acetonitrile:water)

Sources & evidence

ORD record
ord-f9bb846105a0418fa3373ef1e3b3df98
Source dataset
uspto-grants-2013_08
Patent number
US08507488B2

Reaction notes

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