Diethyl Ether → HCID 54671228, compound

HRID 869047Notes

Reaction equation

HRID 869047 reaction equation
C(=O)([O-])OC(C)(C)C[CH:5]([C:15]1C=C[C:18]([C:21]#[C:22][C:23]2[C:28]([N:29](C(OC(C)(C)C)=O)C(OC(C)(C)C)=O)=[N:27][CH:26]=[C:25]([C:44]3[CH:49]=[CH:48][C:47]([S:50]([CH:53]([CH3:55])[CH3:54])(=[O:52])=[O:51])=[CH:46][CH:45]=3)[N:24]=2)=[CH:17][CH:16]=1)[CH2:6][NH:7]C(OC(C)(C)C)=O.[C:60](O)([C:62](F)(F)F)=O.CC[O:69]CC>C(Cl)Cl>[NH2:7][CH2:6][CH:5]([C:15]1[CH:62]=[CH:60][C:18]([C:21]#[C:22][C:23]2[C:28]([NH2:29])=[N:27][CH:26]=[C:25]([C:44]3[CH:49]=[CH:48][C:47]([S:50]([CH:53]([CH3:55])[CH3:54])(=[O:52])=[O:51])=[CH:46][CH:45]=3)[N:24]=2)=[CH:17][CH:16]=1)[OH:69]

Participants

5

Reactant 3

HCID 3283Diethyl EtherHCID 6422Trifluoroacetic acidHCID 131732525HCID 131732525, compound

Product 1

HCID 54671228HCID 54671228, compoundYield 11.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of [1-[4-[2-[3-[bis(tert-butoxycarbonyl)amino]-6-(4-isopropylsulfonylphenyl)pyrazin-2-yl]ethynyl]phenyl]-2-(tert-butoxycarbonylamino)ethyl]tert-butyl carbonate (250.3 mg, 0.2990 mmol) in DCM (2.503 mL) was added TFA (1 mL, 12.98 mmol) and the mixture was stirred at ambient temperature for 18 hours. After this time ether was added to the reaction mixture, the precipitate which resulted was isolated by filtration and dried under vacuum. The filtrate was recombined with precipitate and re-dissolved in DCM. Polymer supported 3-Mercaptopropyl ethyl sulfide was added to the solution and this was left to stir for 15 minutes at ambient temperature. After this time the resin was removed by filtration and washed with DCM. The filtrate was concentrated in vacuo and the material was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]. The fractions were collected, passed through a sodium bicarbonate cartridge to give the titled product as a solid (15.01 mg, 11.5% Yield). 1H NMR (400.0 MHz, DMSO) δ 1.18 (d, J=6.8 Hz, 6H), 2.65 (dd, J=8.1, 12.8 Hz, 2H), 3.45 (t, J=6.8 Hz, 1H), 4.58 (dd, J=3.7, 7.9 Hz, 1H), 5.60 (br s, 1H), 7.15 (s, 2H), 7.43 (d, J=8.3 Hz, 2H), 7.76 (d, J=8.2 Hz, 2H), 7.91 (d, J=8.5 Hz, 2H), 8.24 (d, J=8.5 Hz, 2H) and 8.75 (s, 1H) ppm; MS (ES+) 437.1.

Workup

  1. customthe precipitate which resulted
  2. customwas isolated by filtration
  3. customdried under vacuum
  4. dissolutionre-dissolved in DCM
  5. additionwas added to the solution
  6. waitthis was left
  7. stirringto stir for 15 minutes at ambient temperature
  8. customAfter this time the resin was removed by filtration
  9. washwashed with DCM
  10. concentrationThe filtrate was concentrated in vacuo
  11. customthe material was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]
  12. customThe fractions were collected

Sources & evidence

ORD record
ord-f3116dfe4d5444b6bb7679bc07bd538b
Source dataset
uspto-grants-2015_03
Patent number
US08969356B2

Reaction notes

Loading…