Hydrochloric Acid → HCID 67390574, compound

HRID 1040508Notes

Reaction equation

HRID 1040508 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C:12]1([C:15]([OH:17])=O)[CH2:14][CH2:13]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:42]([O:46][C:47](=[O:60])[NH:48][CH2:49][C:50]1[CH:55]=[CH:54][N:53]=[C:52]([C:56]2([NH2:59])[CH2:58][CH2:57]2)[CH:51]=1)([CH3:45])([CH3:44])[CH3:43].Cl>CN(C=O)C.CCOC(C)=O>[CH2:1]([O:8][C:9](=[O:10])[NH:11][C:12]1([C:15](=[O:17])[NH:59][C:56]2([C:52]3[CH:51]=[C:50]([CH2:49][NH:48][C:47]([O:46][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:60])[CH:55]=[CH:54][N:53]=3)[CH2:58][CH2:57]2)[CH2:13][CH2:14]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 35890121-{[(Benzyloxy)carbonyl]amino}cyclopropane-1-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67390399HCID 67390399, compound

Product 1

HCID 67390574HCID 67390574, compoundYield 56.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

1-Benzyloxycarbonylamino-cyclopropanecarboxylic acid (1.251 g, 5.316 mmol) and HATU (2.527 g, 6.645 mmol) were dissolved in dry DMF (15 mL) and stirred for 5 min. This solution was added to the solution of [2-(1-Amino-cyclopropyl)-pyridin-4-ylmethyl]-carbamic acid tert-butyl ester (2.8 g, 10.633 mmol) in dry DMF (5 mL). TEA (2.2 mL, 16 mmol) was then added and the reaction was stirred at room temperature for 25 min. The reaction was diluted with EtOAc (450 mL) and then acidified with 1N HCl (20 mL) to pH 1. Without separation of the layers, the mixture was basified with saturated NaHCO3 (140 mL) to pH 8.5. Layers were separated. The organic layer was further washed with water (3×350 mL). The organics was dried with anhydrous Na2SO4, filtered, and concentrated to afford 3.73 g of the crude product which was purified by Biotage flash column using 0-2% MeOH/DCM as the gradient to afford 1.447 g of (1-{1-[4-(tert-Butoxycarbonylamino-methyl)-pyridin-2-yl]-cyclopropylcarbamoyl}-cyclopropyl)-carbamic acid benzyl ester as a light brown foam.

Workup

  1. stirringthe reaction was stirred at room temperature for 25 min
  2. customWithout separation of the layers
  3. customLayers were separated
  4. washThe organic layer was further washed with water (3×350 mL)
  5. dry with materialThe organics was dried with anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto afford 3.73 g of the crude product which
  9. customwas purified by Biotage flash column

Sources & evidence

ORD record
ord-21f356e688b24572a63721ca8a1b1025
Source dataset
uspto-grants-2013_10
Patent number
US08552205B2

Reaction notes

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