Trifluoroacetic acid → HCID 71226888, compound

HRID 713435Notes

Reaction equation

HRID 713435 reaction equation
[CH3:1][O:2][C:3]([CH:5]1[CH2:10][CH2:9][N:8]([CH2:11][C:12]([O:14]C(C)(C)C)=O)[CH2:7][CH2:6]1)=[O:4].C(O)(C(F)(F)F)=O.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.[CH:59]1([CH2:62][NH:63][CH2:64][C:65]2[NH:66][C:67](=[O:75])[CH:68]3[CH2:74][O:73][CH2:72][CH2:71][CH:69]3[N:70]=2)[CH2:61][CH2:60]1>ClCCl.CN(C=O)C>[CH3:1][O:2][C:3]([CH:5]1[CH2:6][CH2:7][N:8]([CH2:11][C:12](=[O:14])[N:63]([CH2:62][CH:59]2[CH2:61][CH2:60]2)[CH2:64][C:65]2[NH:66][C:67](=[O:75])[CH:68]3[CH2:74][O:73][CH2:72][CH2:71][CH:69]3[N:70]=2)[CH2:9][CH2:10]1)=[O:4]

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 53742937HCID 53742937, compoundHCID 117819006HCID 117819006, compound

Product 1

HCID 71226888HCID 71226888, compoundYield 73.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-tert-butoxycarbonylmethyl-piperidine-4-carboxylic acid methyl ester (0.65 g, 2.53 mmol, 1 eq.) in 2.5 mL of dichloromethane was added TFA (2.53 mL, 32.8 mmol, 13 eq.). The resulting mixture was stirred at room temperature overnight. After 18 h, the reaction mixture was concentrated and dried under high vacuum. To this oil (0.52 g, 2.22 mmol, 1 eq.) was added DIEA (1.16 mL, 6.66 mmol, 3 eq.) in 5 mL of DMF, followed by HATU (1.69 g, 4.44 mmol, 2 eq.). The resulting mixture was stirred at room temperature for 30 min. 2-[(Cyclopropylmethyl-amino)-methyl]-3,4a,5,7,8,8a-hexahydro-pyrano[4,3-d]pyrimidin-4-one (0.7 g, 2.22 mmol, 1 eq.) in 5 mL of DMF was added and the resulting mixture was stirred at room temperature overnight. After 18 h, the reaction mixture was quenched with H2O (25 mL) and extracted with dichloromethane (3×50 mL). The combined organic layer was concentrated and purified via preparative HPLC (20-100% CH3CN/H2O over 10 min with 0.1% TFA, sun fire C18 OBD 50×50 mm column with flow rate of 60 mL/min) to give the title compound as a white solid (0.69 g). Exact mass calculated for C21H33N4O5 421.2. MS (ESI) m/z 421.6 (M+H)+.

Workup

  1. waitAfter 18 h
  2. concentrationthe reaction mixture was concentrated
  3. customdried under high vacuum
  4. stirringThe resulting mixture was stirred at room temperature for 30 min
  5. stirringthe resulting mixture was stirred at room temperature overnight
  6. waitAfter 18 h
  7. customthe reaction mixture was quenched with H2O (25 mL)
  8. extractionextracted with dichloromethane (3×50 mL)
  9. concentrationThe combined organic layer was concentrated
  10. custompurified via preparative HPLC (20-100% CH3CN/H2O over 10 min with 0.1% TFA, sun fire C18 OBD 50×50 mm column with flow rate of 60 mL/min)

Sources & evidence

ORD record
ord-d1c0644eb0b741b6b2764b9610d08c34
Source dataset
uspto-grants-2015_11
Patent number
US09181266B2

Reaction notes

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