Propargyl alcohol → HCID 89650617, compound

HRID 2174253Notes

Reaction equation

HRID 2174253 reaction equation
N([C:8]1C=C(NC(=O)NCC)N=C[C:9]=1[C:20](O)=[O:21])C1C=CC=CC=1.[NH:23]([C:30]1[CH:35]=[C:34]([NH:36][C:37](=[O:41])[NH:38][CH2:39][CH3:40])[N:33]=[CH:32][C:31]=1[C:42]([NH:44][C:45]1[CH:50]=[CH:49][C:48]([I:51])=[CH:47][CH:46]=1)=[O:43])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(N(CC)CC)C.C(O)C#C>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.CN(C=O)C>[NH:23]([C:30]1[CH:35]=[C:34]([NH:36][C:37](=[O:41])[NH:38][CH2:39][CH3:40])[N:33]=[CH:32][C:31]=1[C:42]([NH:44][C:45]1[CH:46]=[CH:47][C:48]([I:51])=[CH:49][CH:50]=1)=[O:43])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.[CH2:39]([NH:38][C:37]([NH:36][C:34]1[N:33]=[CH:32][C:31]([C:42]([NH:44][C:45]2[CH:46]=[CH:47][C:48]([C:8]#[C:9][CH2:20][OH:21])=[CH:49][CH:50]=2)=[O:43])=[C:30]([NH:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:35]=1)=[O:41])[CH3:40]

Participants

9

Reactant 4

HCID 7859Propargyl alcoholHCID 8471TriethylamineHCID 896500056-(3-Ethylureido)-4-(phenylamino)nicotinic acidHCID 89650743HCID 89650743, compound

Product 2

HCID 89650617HCID 89650617, compoundHCID 89650743HCID 89650743, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

4-anilino-6-(ethylcarbamoylamino)-N-(4-iodophenyl)pyridine-3-carboxamide (i) was prepared by coupling 4-anilino-6-(ethylcarbamoylamino)pyridine-3-carboxylic acid and 4-iodoaniline Compound (i) (50 mg, 0.10 mmol) and PdCl2(PPh3)2 (2.8 mg, 4.0 μmol) were placed in a 0.5-1.5 mL microwave vial and anhydrous DMF (1 mL) added, quickly followed by triethylamine (83 wok 0.60 mmol) and propargyl alcohol (17 μmol, 0.30 mmol). The solution was bubbled with argon for ˜3 minutes then CuI (0.38 mg, 2.0 μmol) was added. The vial was capped and mixture degassed then heated in the microwave at 100° C. for 30 minutes. The mixture was filtered on celite and then the filtrate concentrated in vacuo to give a residue that was purified by flash chromatography, eluting with methanol and DCM. The resulting product mixture was further purified by chromatography (reverse phase; ACN gradient in water), to afford Compound 135. 1H NMR (400 MHz, DMSO) δ 10.40 (br s, 1H), 9.84 (br s, 1H), 9.11 (br s, 1H), 8.57 (s, 1H), 7.94 (br s, 1H), 7.73 (br d, J=8.4 Hz, 2H), 7.45-7.36 (m, 4H), 7.27 (br d, J=7.8 Hz, 3H), 7.15 (m, 1H), 5.33-5.25 (m, 1H), 4.29 (d, J=5.0 Hz, 2H), 3.24-3.04 (m, 2H), 1.06 (t, J=7.2 Hz, 3H), [M+H]+ m/z=430.12.

Workup

  1. customThe solution was bubbled with argon for ˜3 minutes
  2. customThe vial was capped
  3. custommixture degassed
  4. filtrationThe mixture was filtered on celite
  5. concentrationthe filtrate concentrated in vacuo
  6. customto give a residue that
  7. customwas purified by flash chromatography
  8. washeluting with methanol and DCM
  9. customThe resulting product mixture was further purified by chromatography (reverse phase; ACN gradient in water)

Sources & evidence

ORD record
ord-ea87d131713144ab8efc669a64e54aa2
Source dataset
uspto-grants-2015_06
Patent number
US09060515B2

Reaction notes

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