Dimethylformamide → tert-butyl 4-{3-[(3R)-3-{[(1S)-3-tert-butoxy-1-(5-{[3-(2-{[(4-methylphenyl)sulfonyl]oxy}ethoxy)phenyl]ethynyl}pyridin-3-yl)-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate

HRID 526390Notes

Reaction equation

HRID 526390 reaction equation
[C:1]([O:5][C:6](=[O:50])[CH2:7][C@H:8]([NH:24][C:25]([C@@H:27]1[CH2:32][CH2:31][CH2:30][N:29]([C:33](=[O:49])[CH2:34][CH2:35][CH:36]2[CH2:41][CH2:40][N:39]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:38][CH2:37]2)[CH2:28]1)=[O:26])[C:9]1[CH:10]=[N:11][CH:12]=[C:13]([C:15]#[C:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([OH:23])[CH:18]=2)[CH:14]=1)([CH3:4])([CH3:3])[CH3:2].[C:51](=[O:54])([O-])[O-].[Cs+].[Cs+].[CH3:57][C:58]1[CH:63]=[CH:62][C:61]([S:64]([O-:67])(=O)=[O:65])=[CH:60][CH:59]=1.[CH3:68]N(C)C=O>>[C:1]([O:5][C:6](=[O:50])[CH2:7][C@H:8]([NH:24][C:25]([C@@H:27]1[CH2:32][CH2:31][CH2:30][N:29]([C:33](=[O:49])[CH2:34][CH2:35][CH:36]2[CH2:41][CH2:40][N:39]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:38][CH2:37]2)[CH2:28]1)=[O:26])[C:9]1[CH:10]=[N:11][CH:12]=[C:13]([C:15]#[C:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([O:23][CH2:68][CH2:51][O:54][S:64]([C:61]3[CH:62]=[CH:63][C:58]([CH3:57])=[CH:59][CH:60]=3)(=[O:67])=[O:65])[CH:18]=2)[CH:14]=1)([CH3:3])([CH3:2])[CH3:4]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonate2×HCID 85570p-Toluenesulfonate2×HCID 71609226tert-butyl 4-{3-[(3R)-3-{[(1S)-3-tert-butoxy-1-{5-[(3-hydroxyphenyl)ethynyl]pyridin-3-yl}-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate

Product 1

HCID 89407548tert-butyl 4-{3-[(3R)-3-{[(1S)-3-tert-butoxy-1-(5-{[3-(2-{[(4-methylphenyl)sulfonyl]oxy}ethoxy)phenyl]ethynyl}pyridin-3-yl)-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate

Procedure

Tert-butyl 4-{3-[(3R)-3-{[(1S)-3-tert-butoxy-1-{5-[(3-hydroxyphenyl)ethynyl]pyridin-3-yl}-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate (40 mg, 0.06 mmol) was dissolved in N,N-dimethylformamide (6.7 mL). Cesium carbonate (47 mg, 0.15 mmol) and ethane-1,2-diyl bis(4-methylbenzenesulfonate (32 mg, 0.09 mmol) were added. The mixture was stirred at room temperature for 4 hours and stored for 72 hours at 5° C. The addition of cesium carbonate (47 mg, 0.15 mmol) and ethane-1,2-diyl bis(4-methylbenzenesulfonate (32 mg, 0.09 mmol) was repeated and the mixture was stirred at room temperature for 3 hours. The mixture was quenched by addition of saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The combined extracts were washed with brine and dried over sodium sulfate. The solution was concentrated under reduced pressure and the residue was purified by chromatography on silica gel (ethyl acetate in hexane 20% to 100% followed by dioxane in ethyl acetate 0 to 50%) to yield 24 mg of tert-butyl 4-{3-[(3R)-3-{[(1S)-3-tert-butoxy-1-(5-{[3-(2-{[(4-methylphenyl)sulfonyl]oxy}ethoxy)phenyl]ethynyl}pyridin-3-yl)-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate.

Workup

  1. waitstored for 72 hours at 5° C
  2. stirringthe mixture was stirred at room temperature for 3 hours
  3. customThe mixture was quenched by addition of saturated aqueous ammonium chloride solution
  4. extractionextracted with ethyl acetate
  5. washThe combined extracts were washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationThe solution was concentrated under reduced pressure
  8. customthe residue was purified by chromatography on silica gel (ethyl acetate in hexane 20% to 100% followed by dioxane in ethyl acetate 0 to 50%)

Sources & evidence

ORD record
ord-1fa1ec7aa95347b0a58f7c8cb77b1a8d
Source dataset
uspto-grants-2016_05
Patent number
US09345793B2

Reaction notes

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