4-(3-Dimethylamino-2-methoxymethyl-acryloyl)-1H-pyrrole-2-carboxylic Acid (2-hydroxy-1-(S)-phenyl-ethyl)-amide → 4-(5-Methoxymethyl-2-phenylamino-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-(S)-phenyl-ethyl)-amide

HRID 351618Notes

Reaction equation

[OH:1][CH2:2][C@@H:3]([NH:10][C:11]([C:13]1[NH:14][CH:15]=[C:16]([C:18](=O)[C:19]([CH2:24][O:25][CH3:26])=[CH:20]N(C)C)[CH:17]=1)=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[C:28]1([NH:34][C:35]([NH2:37])=[NH:36])[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>CN(C)C(=O)C.C(OCC)(=O)C>[OH:1][CH2:2][C@@H:3]([NH:10][C:11]([C:13]1[NH:14][CH:15]=[C:16]([C:18]2[C:19]([CH2:24][O:25][CH3:26])=[CH:20][N:37]=[C:35]([NH:34][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[N:36]=2)[CH:17]=1)=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

Conditions

Temperature: 90 °C

Procedure

4-(3-Dimethylamino-2-methoxymethyl-acryloyl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-(S)-phenyl-ethyl)-amide (0.27 mmol) was combined with phenyl guanidine (73 mg) in N,N-dimethylacetamide (2 mL) and the resulting suspension was heated at 90° C. for 35 hours. The reaction mixture was diluted with ethyl acetate, washed with saturated NaHCO3 and brine, dried over MgSO4 and concentrated in vacuo. The crude product was purified by prep HPLC (Gilson: Column=CombiHT SB-C189 5 μM, 21.2 mm×100 mm, eluent=0.1% TFA MeCN/H2O gradient) to afford III-a-164 as a yellow solid (3.2 mg). LC/MS(m/z) 444.16 (M+1), 442.19 (M−1); HPLC Method B, Rt=5.16 minutes: 1H NMR consistent with structure.

Workup

washwashed with saturated NaHCO3 and brine
dry with materialdried over MgSO4
concentrationconcentrated in vacuo
customThe crude product was purified by prep HPLC (Gilson: Column=CombiHT SB-C189 5 μM, 21.2 mm×100 mm, eluent=0.1% TFA MeCN/H2O gradient)

Sources & evidence

ORD record: ord-bbd925ebf9f243ea9c0c131e3748fb7b
Source dataset: uspto-grants-2004_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06743791B2

Reaction notes

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