Ethyl Acetate → HCID 136341342, compound

HRID 579319Notes

Reaction equation

HRID 579319 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[C:13]([C:15]2[O:16][C:17]([CH3:20])=[CH:18][N:19]=2)[CH:12]=[C:11]([O:21]C)[C:10]=1[C:23]1[S:27][C:26]([N:28]([CH3:39])[CH:29]2[CH2:34][C:33]([CH3:36])([CH3:35])[NH:32][C:31]([CH3:38])([CH3:37])[CH2:30]2)=[N:25][N:24]=1)C1C=CC=CC=1.CCOC(C)=O>[Pd].CO>[CH3:1][O:8][C:9]1[C:10]([C:23]2[S:27][C:26]([N:28]([CH3:39])[CH:29]3[CH2:34][C:33]([CH3:35])([CH3:36])[NH:32][C:31]([CH3:38])([CH3:37])[CH2:30]3)=[N:25][N:24]=2)=[C:11]([OH:21])[CH:12]=[C:13]([C:15]2[O:16][C:17]([CH3:20])=[CH:18][N:19]=2)[CH:14]=1

Participants

5

Reactant 2

HCID 8857Ethyl AcetateHCID 86727141HCID 86727141, compound

Product 1

HCID 136341342HCID 136341342, compoundYield 39%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A solution of 5-(2-(benzyloxy)-6-methoxy-4-(5-methyloxazol-2-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine (28.9 mg, 0.053 mmol) in 1:1 EtOAc:MeOH (5 mL) was added to a nitrogen flushed flask containing 10% Pd/C (2.9 mg, 10% by weight) and the resulting mixture placed under a hydrogen atmosphere and left to stir at room temperature for 72 hours. The reaction mixture was purged with nitrogen, diluted with EtOAc (10 mL), filtered through celite, then rinsed with EtOAc (50 mL). The filtrate was concentrated in vacuo to afford the crude product as a pale yellow solid. The crude material was purified by preparative HPLC under acidic conditions running a gradient from 20-95% MeCN/water (+0.1% TFA) over 15 minutes. The product containing fractions were loaded directly onto a 1 g SCX cartridge (pre-wet with MeOH) and the cartridge was washed with MeOH (10 mL) then flushed with 7M NH3 in MeOH (10 mL). The MeOH/NH3 was removed in vacuo to afford the title compound as an off-white/pale brown solid (9 mg, 39% yield). LC-MS: Rt 2.08 min; MS m/z 458.4 [M+H]+ [Method B]. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.74 (br. s., 1H), 7.15 (s, 2H), 7.05 (d, J=1.01 Hz, 1H), 4.42-4.33 (m, 1H), 4.04 (s, 3H), 3.03 (s, 3H), 2.41 (d, J=1.01 Hz, 3H), 1.64 (dd, J=11.87, 3.28 Hz, 2H), 1.44 (t, J=12.13 Hz, 2H), 1.22 (s, 6H), 1.09 (s, 6H).

Workup

  1. waitleft
  2. customThe reaction mixture was purged with nitrogen
  3. additiondiluted with EtOAc (10 mL)
  4. filtrationfiltered through celite
  5. washrinsed with EtOAc (50 mL)
  6. concentrationThe filtrate was concentrated in vacuo
  7. customto afford the crude product as a pale yellow solid
  8. customThe crude material was purified by preparative HPLC under acidic conditions
  9. customover 15 minutes
  10. additionThe product containing fractions
  11. washthe cartridge was washed with MeOH (10 mL)
  12. customthen flushed with 7M NH3 in MeOH (10 mL)
  13. customThe MeOH/NH3 was removed in vacuo

Sources & evidence

ORD record
ord-4d05dc6ee7a842228e6d0c9a1d7fbe2c
Source dataset
uspto-grants-2015_05
Patent number
US09040712B2

Reaction notes

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