Phenol → (2S,4R)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-N-(4-(4-fluorophenoxy)phenyl)-4-phenoxypyrrolidine-2-carboxamide

HRID 1630278Notes

Reaction equation

CC(OC(/N=N/C(OC(C)C)=O)=O)C.[N:15]1([CH2:20][C:21]([N:23]2[CH2:27][C@H:26]([OH:28])[CH2:25][C@H:24]2[C:29]([NH:31][C:32]2[CH:37]=[CH:36][C:35]([O:38][C:39]3[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=3)=[CH:34][CH:33]=2)=[O:30])=[O:22])[CH:19]=[N:18][CH:17]=[N:16]1.[C:46]1(O)[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[N:15]1([CH2:20][C:21]([N:23]2[CH2:27][C@H:26]([O:28][C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=3)[CH2:25][C@H:24]2[C:29]([NH:31][C:32]2[CH:33]=[CH:34][C:35]([O:38][C:39]3[CH:40]=[CH:41][C:42]([F:45])=[CH:43][CH:44]=3)=[CH:36][CH:37]=2)=[O:30])=[O:22])[CH:19]=[N:18][CH:17]=[N:16]1

Participants

Conditions

Temperature: 60 °C

Procedure

Diisopropylazodicarboxylate (0.111 mL, 0.551 mmol) was added to a flask charged with (2S,4R)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-N-(4-(4-fluorophenoxy)phenyl)-4-hydroxypyrrolidine-2-carboxamide (233 mg, 0.551 mmol), prepared as in Reference 11, phenol (52 mg, 0.55 mmol), triphenylphosphine (145 mg, 0.551 mmol) and THF (3 mL). The reaction mixture was heated at 60° C. for 30 minutes and then concentrated. Product was purified from the residue by reverse phase HPLC to give Compound 259, (2S,4R)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-N-(4-(4-fluorophenoxy)phenyl)-4-phenoxypyrrolidine-2-carboxamide (15 mg, 0.012 mmol, 5% yield), as an off-white solid. 1H-NMR (400 MHz, DMSO-d6): 10.17 (s, 1H), 8.45 (s, 1H), 7.94 (s, 1H), 7.58 (d, J=8.8 Hz, 2H), 7.37-7.32 (m, 2H), 7.21-7.17 (m, 2H), 7.04-6.95 (m, 7H). MS (EI) for C27H24FN5O4. found 502.3 (MH+).

Workup

concentrationconcentrated
customProduct was purified from the residue by reverse phase HPLC

Sources & evidence

ORD record: ord-dd43890812e44814ba06c01a413f17a9
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08791102B2

Reaction notes

Loading…