Acetonitrile → HCID 59293919, compound

HRID 1930786Notes

Reaction equation

HRID 1930786 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[O:7][CH2:8][C:9]1[CH:27]=[CH:26][C:12]([CH2:13][C:14]2[CH:18]=[C:17]([C:19]3[C:20]([NH2:25])=[N:21][CH:22]=[CH:23][CH:24]=3)[O:16][N:15]=2)=[CH:11][CH:10]=1.C(#N)C.[CH3:31][N:32]([CH3:52])[CH2:33][CH2:34][O:35][C:36](=[O:51])[C@@H:37]([NH:43][C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH2:38][CH2:39][C:40](O)=[O:41].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>O>[CH3:52][N:32]([CH3:31])[CH2:33][CH2:34][O:35][C:36](=[O:51])[C@@H:37]([NH:43][C:44]([O:46][C:47]([CH3:48])([CH3:49])[CH3:50])=[O:45])[CH2:38][CH2:39][C:40](=[O:41])[NH:25][C:20]1[C:19]([C:17]2[O:16][N:15]=[C:14]([CH2:13][C:12]3[CH:26]=[CH:27][C:9]([CH2:8][O:7][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=4)=[CH:10][CH:11]=3)[CH:18]=2)=[CH:24][CH:23]=[CH:22][N:21]=1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 16719049E-1210HCID 86641183HCID 86641183, compound

Product 1

HCID 59293919HCID 59293919, compoundYield 20.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a mixture of (S)-2-tert-butoxycarbonylamino-pentanedioic acid 5-benzyl ester 1-(2-dimethylamino-ethyl)ester (370 mg, 0.70 mmol; 77% purity) described in Manufacturing Example 3-1 and ethanol (4 mL) was added palladium-carbon (40 mg, 0.19 mmol; 50% water content) at room temperature, which was stirred overnight at room temperature under a hydrogen atmosphere (1 atm). The reaction mixture was replaced with nitrogen and filtered through a Celite pad. The solvent was evaporated under a reduced pressure, so as to obtain (S)-2-tert-butoxycarbonylamino-pentanedioic acid 1-(2-dimethylamino-ethyl)ester (300 mg) in a crude form. The crude product thus obtained was used directly in the next reaction. To a mixture of 3-(3-(4-(pyridin-2-yloxymethyl)-benzyl)-isoxazol-5-yl)-pyridin-2-ylamine (150 mg, 0.42 mmol) described in Reference Example 1 and acetonitrile (3 mL) were added (S)-2-tert-butoxycarbonylamino-pentanedioic acid 1-(2-dimethylamino-ethyl)ester (crude, 190 mg) and O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl-uronium hexafluorophosphate (160 mg, 0.42 mmol) in this order at 0° C., which was stirred overnight at room temperature. Water was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with saturated brine, and the solvent was evaporated under a reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate:methanol=30:1), so as to obtain the titled compound (56 mg, purity of 75%).

Workup

  1. customwas used directly in the next reaction
  2. extractionwas extracted with ethyl acetate
  3. washThe organic layer was washed with saturated brine
  4. customthe solvent was evaporated under a reduced pressure
  5. customThe residue was purified by NH silica gel column chromatography (ethyl acetate:methanol=30:1)

Sources & evidence

ORD record
ord-20eae1b017314818812702a6d8a157ee
Source dataset
uspto-grants-2012_05
Patent number
US08188119B2

Reaction notes

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