Propargyl alcohol → HCID 57405010, compound

HRID 1520083Notes

Reaction equation

HRID 1520083 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]3[N:12]=[N:13][N:14]([C:16]4[CH:21]=[CH:20][C:19]([C:22]([N:24]5[CH2:29][CH2:28][O:27][CH2:26][CH2:25]5)=[O:23])=[CH:18][CH:17]=4)[CH:15]=3)=[N:7][NH:8]2)=[CH:4][CH:3]=1.[CH2:30]([OH:33])[C:31]#[CH:32]>N1CCCC1.C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N:24]1([C:22]([C:19]2[CH:18]=[CH:17][C:16]([N:14]3[CH:15]=[C:11]([C:6]4[C:5]5[C:9](=[CH:10][C:2]([C:32]#[C:31][CH2:30][OH:33])=[CH:3][CH:4]=5)[NH:8][N:7]=4)[N:12]=[N:13]3)=[CH:21][CH:20]=2)=[O:23])[CH2:25][CH2:26][O:27][CH2:28][CH2:29]1

Participants

6

Reactant 2

HCID 7859Propargyl alcoholHCID 57405511HCID 57405511, compound

Product 1

HCID 57405010HCID 57405010, compoundYield 28.3%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolventHCID 31268PyrrolidineSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of {4-[4-(6-Bromo-1H-indazol-3-yl)-[1,2,3]triazol-1-yl]-phenyl}-morpholin-4-yl-methanone (150 mg; 0.33 mmol; 1.0 eq.), propargyl alcohol (39 μl; 0.66 mmol; 2.0 eq.) and Pd(PPh3)4 (19 mg, 0.02 mmol, 0.05 eq.) in pyrrolidine (1.5 mL) was heated O/N at 80° C. in a sealed tube. The reaction mixture was then diluted with DCM and washed with a saturated solution of NH4Cl (three times) and brine. Organic phase was dried over magnesium sulfate, filtered and concentrated. Purification by preparative HPLC gave the title compound as a beige solid (40 mg, 28%). 1H NMR (300 MHz, DMSO-d6-d6): 13.50 (brs, 1H), 9.42 (s, 1H), 8.34 (dd, J=8.5 Hz, 1.0 Hz, 1H), 8.15 (d, J=8.6 Hz, 2H), 7.70-7.67 (m, 3H), 7.28 (dd, J=8.5 Hz, 1.0 Hz, 1H), 5.40 (t, J=6.0 Hz, 1H), 4.35 (d, J=6.0 Hz, 2H), 3.64 (m, 6H), 3.47 (m, 2H).

Workup

  1. washwashed with a saturated solution of NH4Cl (three times) and brine
  2. dry with materialOrganic phase was dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-3eb2215a599249a1aa905ef4e7a3cb17
Source dataset
uspto-grants-2015_07
Patent number
US09073892B2

Reaction notes

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