Diisopropylethylamine → [(3R,4S)-3-[(R)-2-(tert-Butyl-dimethyl-silanyloxy)-1-(5-chloro-pyridin-2-yloxy)-ethyl]-4-(3,4-dichloro-phenyl)-pyrrolidin-1-yl]-(6-methyl-pyridazin-4-yl)-methanone

HRID 906937Notes

Reaction equation

HRID 906937 reaction equation
[C:1]([Si:5]([CH3:31])([CH3:30])[O:6][CH2:7][C@@H:8]([C@@H:17]1[C@@H:21]([C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([Cl:29])[CH:23]=2)[CH2:20][NH:19][CH2:18]1)[O:9][C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][N:11]=1)([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:65][C:66]1[N:71]=[N:70][CH:69]=[C:68]([C:72](O)=[O:73])[CH:67]=1>CN(C=O)C.C(OCC)(=O)C>[C:1]([Si:5]([CH3:31])([CH3:30])[O:6][CH2:7][C@@H:8]([C@@H:17]1[C@@H:21]([C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([Cl:29])[CH:23]=2)[CH2:20][N:19]([C:72]([C:68]2[CH:67]=[C:66]([CH3:65])[N:71]=[N:70][CH:69]=2)=[O:73])[CH2:18]1)[O:9][C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][N:11]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 553007686-Methyl-4-pyridazinecarboxylic acid hydrochlorideHCID 671315312-{(R)-2-(tert-Butyl-dimethyl-silanyloxy)-1-[(3R,4S)-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-ethoxy}-5-chloro-pyridine

Product 1

HCID 67131632[(3R,4S)-3-[(R)-2-(tert-Butyl-dimethyl-silanyloxy)-1-(5-chloro-pyridin-2-yloxy)-ethyl]-4-(3,4-dichloro-phenyl)-pyrrolidin-1-yl]-(6-methyl-pyridazin-4-yl)-methanoneYield 27.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-{(R)-2-(tert-butyl-dimethyl-silanyloxy)-1-[(3R,4S)-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-ethoxy}-5-chloro-pyridine (220 mg) in DMF (12 mL)at −20° C. were added Hunig base (0.132 mL, 0.78 mmol) and then HATU (202 mg) and then 6-methyl-pyridazine-4-carboxylic acid (0.78 mmol, described herein above). The mixture was diluted with ethyl acetate and washed with aq.ammonium chloride solution three times and aq. sodium bicarbonate solution. The separated organic phase was dried over sodium sulfate and concentrated in vaccuo after filtration. The residue was purified by TLC (SiO2, MeOH/DCM, 1:10) yielded 74 mg (27%) of the title compound as a light yellow oil. ES-MS m/e: 623.3 (M+H+).

Workup

  1. washwashed with aq
  2. dry with materialThe separated organic phase was dried over sodium sulfate
  3. concentrationconcentrated in vaccuo
  4. filtrationafter filtration
  5. customThe residue was purified by TLC (SiO2, MeOH/DCM, 1:10)

Sources & evidence

ORD record
ord-41deab3745d34fd8adfe49badc077ce0
Source dataset
uspto-grants-2011_09
Patent number
US08012998B2

Reaction notes

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