Triphenylphosphine → HCID 59451383, compound

HRID 1874808Notes

Reaction equation

HRID 1874808 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([O:13]CC)=O)=[CH:5]2.[N:16]1([CH2:22][CH2:23]O)[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O.[NH2:60][CH2:61][C:62]1[C:63]([F:79])=[C:64]([O:69][C:70]2[CH:71]=[C:72]([CH:75]=[C:76]([Cl:78])[CH:77]=2)[C:73]#[N:74])[C:65]([Cl:68])=[CH:66][CH:67]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C1COCC1.CO.CN(C=O)C>[Cl:68][C:65]1[CH:66]=[CH:67][C:62]([CH2:61][NH:60][C:11]([C:6]2[NH:7][C:8]3[C:4]([CH:5]=2)=[CH:3][C:2]([O:1][CH2:23][CH2:22][N:16]2[CH2:17][CH2:18][O:19][CH2:20][CH2:21]2)=[CH:10][CH:9]=3)=[O:13])=[C:63]([F:79])[C:64]=1[O:69][C:70]1[CH:71]=[C:72]([C:73]#[N:74])[CH:75]=[C:76]([Cl:78])[CH:77]=1

Participants

11

Reactant 7

HCID 11776TriphenylphosphineHCID 611632-MorpholinoethanolHCID 81531DiisopropylethylamineHCID 90677Ethyl 5-hydroxy-1H-indole-2-carboxylateHCID 97268Di-tert-butyl azodicarboxylateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 594513923-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile

Product 1

HCID 59451383HCID 59451383, compoundYield 3.2%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

In a 24-well Bohdan block, ethyl 5-hydroxy-1H-indole-2-carboxylate (0.100 g, 0.487 mmol), 2-(4-morpholinyl)ethanol (0.160 g, 1.22 mmol) and PS-triphenylphosphine (406 mg, 1.22 mmol) were dissolved in THF (1 mL). Di-tert-butyl azodicarboxylate (1.22 M in THF, 1 mL) was added and the block shaken overnight. The reactor block was drained into a second Bohdan block and rinsed with THF. 1 N LiOH (1 mL) was added and the reactor block shaken for 6 hours at RT. 1 N HCl (1 mL) was added and the block was drained into a 24-well plate, rinsed with THF and the solvent evaporated. The residue was dissolved in DMF and filtered to remove salts. To the DMF solution was added 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (50 mg, 0.161 mmol) followed by HATU (61.1 mg, 0.161 mmol) and DIPEA (30 μL, 0.222 mmol) and the reaction mixture stirred overnight. The resulting solution was diluted to 2 mL with MeOH. Purification was accomplished by Reverse-Phase HPLC (water/acetonitrile with 0.1% TFA) to afford the title compound (0.003 g, 1%) as a glass. 1H NMR (400 MHz, CDCl3): δ ppm 9.05-9.11 (m, 1H), 7.35-7.37 (m, 1H), 7.34 (s, 1H), 7.27-7.31 (m, 2H), 7.15-7.18 (m, 1H), 7.05 (d, 1H), 7.02 (dd, 1H), 6.99 (dd, 1H), 6.79 (d, 1H), 6.50-6.57 (m, 1H), 4.73 (d, 2H), 4.13-4.18 (m, 2H), 3.72-3.79 (m, 4H), 2.82-2.90 (m, 2H), 2.60-2.69 (m, 4H). LCMS m/z 583.1 (M+1).

Workup

  1. washrinsed with THF
  2. addition1 N LiOH (1 mL) was added
  3. stirringthe reactor block shaken for 6 hours at RT
  4. addition1 N HCl (1 mL) was added
  5. washrinsed with THF
  6. customthe solvent evaporated
  7. dissolutionThe residue was dissolved in DMF
  8. filtrationfiltered
  9. customto remove salts
  10. stirringthe reaction mixture stirred overnight
  11. customPurification

Sources & evidence

ORD record
ord-e29e71ccb4e74d0986398829ad186270
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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