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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 351618
Notes
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Reaction equation

HRID 351618 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
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 2

HCID 865879764-(3-Dimethylamino-2-methoxymethyl-acryloyl)-1H-pyrrole-2-carboxylic Acid (2-hydroxy-1-(S)-phenyl-ethyl)-amideHCID 178418923HCID 178418923, compound

Product 1

HCID 600906024-(5-Methoxymethyl-2-phenylamino-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-(S)-phenyl-ethyl)-amideYield 2.7%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolvent
HCID 31374
Dimethylacetamide
Solvent

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

  1. washwashed with saturated NaHCO3 and brine
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated in vacuo
  4. 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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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes