Triethylamine → (2S)-2-(tert-Butoxy)-2-{4,23-dimethyl-22-oxa-1,5,7,8-tetraazapentacyclo[21.2.2.16,9.02,7.013,18]octacosa-2,4,6(28),8,13(18),14,16-heptaen-3-yl}acetic acid

HRID 921106Notes

Reaction equation

HRID 921106 reaction equation
[C:1]([O:5][C@@H:6]([C:10]1[C:34]([CH3:35])=[N:33][C:32]2=[CH:36][C:29]3=[N:30][N:31]2[C:11]=1[N:12]1[CH2:38][CH2:37][C:15]([CH3:39])([O:16][CH2:17][CH:18]=[CH:19][C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:25]=2[CH2:26][CH:27]=[CH:28]3)[CH2:14][CH2:13]1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C>CO.[Pd]>[C:1]([O:5][C@@H:6]([C:10]1[C:34]([CH3:35])=[N:33][C:32]2=[CH:36][C:29]3=[N:30][N:31]2[C:11]=1[N:12]1[CH2:13][CH2:14][C:15]([CH3:39])([O:16][CH2:17][CH2:18][CH2:19][C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:25]=2[CH2:26][CH2:27][CH2:28]3)[CH2:37][CH2:38]1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 8471TriethylamineHCID 123749244(2S)-2-(tert-Butoxy)-2-[4,23-dimethyl-22-oxa-1,5,7,8-tetraazapentacyclo[21.2.2.16,9.02,7.013,18]octacosa-2,4,6(28),8,10,13(18),14,16,19-nonaen-3-yl]acetic acid

Product 1

HCID 118318790(2S)-2-(tert-Butoxy)-2-{4,23-dimethyl-22-oxa-1,5,7,8-tetraazapentacyclo[21.2.2.16,9.02,7.013,18]octacosa-2,4,6(28),8,13(18),14,16-heptaen-3-yl}acetic acidYield 41.3%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a solution of the (2S)-2-(tert-butoxy)-2-[4,23-dimethyl-22-oxa-1,5,7,8-tetraazapentacyclo[21.2.2.16,9.02,7.013,18]octacosa-2,4,6(28),8,10,13(18),14,16,19-nonaen-3-yl]acetic acid (21 mg, 0.040 mmol) and triethylamine (5.52 μl, 0.040 mmol) in MeOH (2 mL) was added palladium on carbon (0.42 mg, 3.96 μmol). The mixture was flushed with hydrogen then stirred under a hydrogen balloon. After 1 h, the mixture was filtered over celite rinsing with MeOH then concentrated. The crude material was purified via preparative HPLC to give the title compound (9.1 mg, 0.016 mmol, 41.3% yield). 1H NMR (500 MHz, DMSO-d6) δ 7.21 (d, J=3.4 Hz, 2H), 7.14 (d, J=3.7 Hz, 2H), 6.30 (s, 1H), 5.86 (s, 1H), 4.74-4.59 (m, 1H), 3.77 (t, J=11.4 Hz, 1H), 3.52 (d, J=1.8 Hz, 3H), 3.22-2.94 (m, 5H), 2.90 (s, 3H), 2.72-2.58 (m, 2H), 2.37-2.20 (m, 1H), 2.00-1.54 (m, 7H), 1.38 (s, 1H), 1.17 (br. s., 9H). LCMS (M+H) calcd for C31H43N4O4: 535.32. found: 535.5.

Workup

  1. customThe mixture was flushed with hydrogen
  2. filtrationthe mixture was filtered
  3. washover celite rinsing with MeOH
  4. concentrationthen concentrated
  5. customThe crude material was purified via preparative HPLC

Sources & evidence

ORD record
ord-a6ae9a258d5b462b8599af997ac7018e
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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