Triphenylphosphine → tert-butyl 4-{3-[(3R)-3-{[(1S)-1-{5-[(3-cyano-4-fluorobenzyl)oxy]pyridin-3-yl}-3-methoxy-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate

HRID 526350Notes

Reaction equation

HRID 526350 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:20]([O:24][C:25]([N:27]1[CH2:32][CH2:31][CH:30]([CH2:33][CH2:34][C:35]([N:37]2[CH2:42][CH2:41][CH2:40][C@@H:39]([C:43](=[O:58])[NH:44][C@H:45]([C:51]3[CH:52]=[N:53][CH:54]=[C:55]([OH:57])[CH:56]=3)[CH2:46][C:47]([O:49][CH3:50])=[O:48])[CH2:38]2)=[O:36])[CH2:29][CH2:28]1)=[O:26])([CH3:23])([CH3:22])[CH3:21].[F:59][C:60]1[CH:67]=[CH:66][C:65]([CH2:68]O)=[CH:64][C:61]=1[C:62]#[N:63].N(C(OC(C)C)=O)=NC(OC(C)C)=O>ClCCl.C1COCC1>[C:62]([C:61]1[CH:64]=[C:65]([CH:66]=[CH:67][C:60]=1[F:59])[CH2:68][O:57][C:55]1[CH:56]=[C:51]([C@@H:45]([NH:44][C:43]([C@@H:39]2[CH2:40][CH2:41][CH2:42][N:37]([C:35](=[O:36])[CH2:34][CH2:33][CH:30]3[CH2:29][CH2:28][N:27]([C:25]([O:24][C:20]([CH3:23])([CH3:21])[CH3:22])=[O:26])[CH2:32][CH2:31]3)[CH2:38]2)=[O:58])[CH2:46][C:47]([O:49][CH3:50])=[O:48])[CH:52]=[N:53][CH:54]=1)#[N:63]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 27739342-Fluoro-5-(hydroxymethyl)benzonitrileHCID 71259055tert-butyl-4-{3-[(3R)-3-{[(1S)-1-(5-hydroxypyridin-3-yl)-3-methoxy-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate

Product 1

HCID 71259840tert-butyl 4-{3-[(3R)-3-{[(1S)-1-{5-[(3-cyano-4-fluorobenzyl)oxy]pyridin-3-yl}-3-methoxy-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylateYield 7.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Polymer bound triphenylphosphine (30 mg) and tert-butyl-4-{3-[(3R)-3-{[(1S)-1-(5-hydroxypyridin-3-yl)-3-methoxy-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate (example 5e, 30 mg, 60 μmol) were stirred in dichloromethane for 30 minutes. 2-Fluoro-5-(hydroxymethyl)benzonitrile (26 mg, 0.17 mmol) in THF was added and the mixture was cooled to 0° C. Dipropan-2-yl diazene-1,2-dicarboxylate (20 μL, 0.11 mmol) was added, the mixture was stirred for 3 hours at room temperature and then stored for 16 hours at 5° C. After filtration the filtrate was concentrated under reduced pressure and the residue was purified by preparative thin layer chromatography on silica gel (ethyl acetate 100%) to yield 3.2 mg of tert-butyl 4-{3-[(3R)-3-{[(1S)-1-{5-[(3-cyano-4-fluorobenzyl)oxy]pyridin-3-yl}-3-methoxy-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate.

Workup

  1. waitstored for 16 hours at 5° C
  2. filtrationAfter filtration the filtrate
  3. concentrationwas concentrated under reduced pressure
  4. customthe residue was purified by preparative thin layer chromatography on silica gel (ethyl acetate 100%)

Sources & evidence

ORD record
ord-6e725c24c0a649d2aafe085ef6637ea5
Source dataset
uspto-grants-2016_05
Patent number
US09345793B2

Reaction notes

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