HCID 86638798, compound → HCID 59180175, compound

HRID 601903Notes

Reaction equation

HRID 601903 reaction equation
[CH2:1]([C:3]1[C:4]2[CH2:21][CH2:20][C:19](=O)[C:5]=2[N:6]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[C:7]=1[C:8]([OH:10])=[O:9])C.O=[C:24]1[C:28]2[NH:29][C:30]([C:32]([O:34][CH2:35][CH3:36])=[O:33])=[CH:31][C:27]=2[CH2:26][CH2:25]1.[CH3:37][Mg]Br>>[CH3:1][CH:24]1[C:28]2[NH:29][C:30]([C:32]([O:34][CH2:35][CH3:36])=[O:33])=[CH:31][C:27]=2[CH2:26][CH2:25]1.[CH3:37][C:19]1[C:5]2[N:6]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:16])[CH3:17])[C:7]([C:8]([O:10][CH2:24][CH3:25])=[O:9])=[CH:3][C:4]=2[CH2:21][CH:20]=1

Participants

4

Reactant 2

HCID 86638798HCID 86638798, compoundHCID 178418573HCID 178418573, compound

Product 2

HCID 59180175HCID 59180175, compoundHCID 66873715HCID 66873715, compound

Procedure

The title compound was synthesized from SEM-protected ethyl 6-oxo-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate (ethyl 6-oxo-1-((2-(trimethylsilyl)ethoxy)methyl)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate) (0.5 g, 2.79 mmol) and methylmagnesium bromide (4.85 mL, 6.8 mmol, 1.4 M in toluene, 2.2 equiv) according to General Procedure 3 to give ethyl 6-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1,4-dihydrocyclopenta[b]pyrrole-2-carboxylate. The ethyl 6-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1,4-dihydrocyclopenta[b]pyrrole-2-carboxylate was then deprotected according to General Procedure 10.3 to provide ethyl 6-methyl-1,4-dihydrocyclopenta[b]pyrrole-2-carboxylate, which was subjected to hydrogenation according to General Procedure 6. The crude product was purified by preparative HPLC using the Chromeleon purification system. A 0.1% formic acid/1% acetonitrile mixture in water (aqueous phase) and methanol (no modifier added—organic phase) using a 50 mm Dynamax HPLC C-18 column at 28 mL/min (initial gradient of 60% methanol and increasing to 100% over 7 minutes) afforded the title compound (20.8 mg, 47%). LCMS m/e 216 (M+Na). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.24 (d, J=6.83 Hz, 3H), 1.35 (t, J=7.11 Hz, 3H), 1.90-2.02 (m, 1H), 2.50-2.70 (m, 3H), 3.08-3.20 (m, J=6.92, 6.92, 6.92, 6.92, 6.77 Hz, 1H), 4.30 (qd, J=7.12, 1.39 Hz, 2H), 6.65 (d, J=1.64 Hz, 1H), 8.72 (br. s, 1H).

Sources & evidence

ORD record
ord-f2d449ab0f614048b4b0fda7ed89af51
Source dataset
uspto-grants-2011_03
Patent number
US07902252B2

Reaction notes

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