Diisopropylethylamine → (S)-5-({[6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazine-3-carbonyl]-amino}-methyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester

HRID 1972050Notes

Reaction equation

HRID 1972050 reaction equation
[CH2:1]([C:5]1[N:10]=[N:9][C:8]([C:11]([OH:13])=O)=[CH:7][C:6]=1[C:14]1[CH:19]=[CH:18][C:17]([O:20][CH:21]2[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)=[CH:16][CH:15]=1)[CH2:2][CH2:3][CH3:4].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:51]([O:55][C:56]([N:58]1[CH2:62][C@H:61]([CH2:63][NH2:64])[O:60][C:59]1([CH3:66])[CH3:65])=[O:57])([CH3:54])([CH3:53])[CH3:52].CCN(C(C)C)C(C)C>CN(C=O)C.CCOCC.O>[C:51]([O:55][C:56]([N:58]1[CH2:62][C@H:61]([CH2:63][NH:64][C:11]([C:8]2[N:9]=[N:10][C:5]([CH2:1][CH2:2][CH2:3][CH3:4])=[C:6]([C:14]3[CH:15]=[CH:16][C:17]([O:20][CH:21]4[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26]4)=[CH:18][CH:19]=3)[CH:7]=2)=[O:13])[O:60][C:59]1([CH3:66])[CH3:65])=[O:57])([CH3:54])([CH3:53])[CH3:52]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 673720716-Butyl-5-(4-cyclohexyloxy-phenyl)-pyridazine-3-carboxylic acidHCID 67373621(S)-5-aminomethyl-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester

Product 1

HCID 67373730(S)-5-({[6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazine-3-carbonyl]-amino}-methyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of 6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazine-3-carboxylic acid (Example 93, 0.34 mmol, 0.12 g), HBTU (0.34 mmol, 0.13 g) and (S)-5-aminomethyl-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (0.34 mmol, 0.05 mL) in DMF was added DIEA (1.0 mmol, 0.17 mL). Upon completion of the reaction, the mixture was diluted with ether, and then poured into water. The resulting mixture was extracted, the organic layer was dried. The solvent was removed, and the resulting residue was chromatographed with 4:1 hexane/EtOAc to provide (S)-5-({[6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazine-3-carbonyl]-amino}-methyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester was used as is in the next step. LCMS: m/z 566.9 [M+1].

Workup

  1. customUpon completion of the reaction
  2. extractionThe resulting mixture was extracted
  3. customthe organic layer was dried
  4. customThe solvent was removed
  5. customthe resulting residue was chromatographed with 4:1 hexane/EtOAc

Sources & evidence

ORD record
ord-efb4df4473d544a29b88060d1495a861
Source dataset
uspto-grants-2013_04
Patent number
US08431575B2

Reaction notes

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