HCID 118318825, compound → HCID 118318828, compound

HRID 921157Notes

Reaction equation

HRID 921157 reaction equation
[C:1]([O:5][C@@H:6]([C:10]1[C:37]([CH3:38])=[N:36][C:35]2=[CH:39][C:32]3=[N:33][N:34]2[C:11]=1[N:12]1[CH2:43][CH2:42][C:15]([CH3:44])([O:16][CH2:17][CH2:18][CH2:19][CH2:20][C@H:21]([CH3:41])[O:22][C:23]2[CH:24]=[C:25]([F:40])[CH:26]=[CH:27][C:28]=2[CH2:29][CH:30]=[CH:31]3)[CH2:14][CH2:13]1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:3])[CH3:2]>C(OCC)(=O)C.[Pd]>[C:1]([O:5][C@@H:6]([C:10]1[C:37]([CH3:38])=[N:36][C:35]2=[CH:39][C:32]3=[N:33][N:34]2[C:11]=1[N:12]1[CH2:13][CH2:14][C:15]([CH3:44])([O:16][CH2:17][CH2:18][CH2:19][CH2:20][C@H:21]([CH3:41])[O:22][C:23]2[CH:24]=[C:25]([F:40])[CH:26]=[CH:27][C:28]=2[CH2:29][CH2:30][CH2:31]3)[CH2:42][CH2:43]1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 1

HCID 118318825HCID 118318825, compound

Product 1

HCID 118318828HCID 118318828, compoundYield 73.5%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of (2S)-2-(tert-butoxy)-2-[(10E,20S)-16-fluoro-4,20,26-trimethyl-19,25-dioxa-1,5,7,8-tetraazapentacyclo[24.2.2.16,9.02,7.013,18]hentriaconta-2,4,6(31),8,10,13(18),14,16-octaen-3-yl]acetic acid (30 mg, 0.049 mmol) in ethyl acetate (1.5 mL) was added 10% Pd/C (5.24 mg, 4.93 μmol) and the resulting mixture was stirred under hydrogen balloon atmosphere for 16 h. At this point LCMS indicates completion of reaction. Mixture was then filtered and concentrated to afford (2S)-2-(tert-butoxy)-2-[(20S)-16-fluoro-4,20,26-trimethyl-19,25-dioxa-1,5,7,8-tetraazapentacyclo[24.2.2.16,9.02,7.013,18]hentriaconta-2,4,6(31),8,13(18),14,16-heptaen-3-yl]acetic acid (23 mg, 0.036 mmol, 72.6% yield) as white solid. 1H NMR (600 MHz, DMSO-d6) δ 7.14 (t, J=7.5 Hz, 1H), 6.88 (d, J=11.4 Hz, 1H), 6.61 (t, J=7.7 Hz, 1H), 6.23 (s, 1H), 5.62 (br. s., 1H), 4.60 (br. s., 1H), 4.31 (t, J=12.1 Hz, 1H), 2.79-2.73 (m, 1H), 2.70 (t, J=8.1 Hz, 2H), 2.56 (d, J=11.4 Hz, 1H), 2.46 (s, 3H), 2.20 (br. s., 1H), 1.91 (s, 1H), 1.84-1.75 (m, 3H), 1.70-1.62 (m, 5H), 1.56-1.44 (m, 3H), 1.18 (d, J=5.5 Hz, 3H), 1.16 (s, 3H), 1.13 (s, 9H). 4 piperidine hydrogens are missing. LCMS (M+H)=611.4.

Workup

  1. customcompletion of reaction
  2. filtrationMixture was then filtered
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-ccd761419fa040edb77f0c366109a235
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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