Pyridine → N-(2,2-dimethyl-1(S)-methylcarbamoylpropyl)-3(R)-(3-pyridin-4-yl-1H-pyrrol-1-yl)succinamic acid benzyl ester

HRID 566743Notes

Reaction equation

HRID 566743 reaction equation
FC(F)(F)C(O)=O.[CH2:8]([O:15][C:16](=[O:32])[CH2:17][C@@H:18]([NH2:31])[C:19]([NH:21][C@H:22]([C:27](=[O:30])[NH:28][CH3:29])[C:23]([CH3:26])([CH3:25])[CH3:24])=[O:20])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.CO[CH:35]1[CH:39]([C:40]2[CH:45]=[CH:44][N:43]=[CH:42][CH:41]=2)[CH2:38][CH:37](OC)O1.N1C=CC=CC=1.Cl[Si](C)(C)C>ClCCCl>[CH2:8]([O:15][C:16](=[O:32])[CH2:17][C@@H:18]([N:31]1[CH:37]=[CH:38][C:39]([C:40]2[CH:45]=[CH:44][N:43]=[CH:42][CH:41]=2)=[CH:35]1)[C:19]([NH:21][C@H:22]([C:27](=[O:30])[NH:28][CH3:29])[C:23]([CH3:25])([CH3:26])[CH3:24])=[O:20])[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 6397ChlorotrimethylsilaneHCID 183802894-(2,5-Dimethoxy-tetrahydro-furan-3-yl)pyridineHCID 700814343(r)-Amino-n-(2,2-dimethyl-1(s)-(methylcarbamoyl)propyl)succinamic acid benzyl ester trifluoroacetate salt

Product 1

HCID 15459669N-(2,2-dimethyl-1(S)-methylcarbamoylpropyl)-3(R)-(3-pyridin-4-yl-1H-pyrrol-1-yl)succinamic acid benzyl esterYield 43%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A solution of crude 3(R)-amino-N-(2,2-dimethyl-1(S)-methylcarbamoylpropyl)succinamic acid benzyl ester trifluoroacetate salt (0.44 mmol), 4-(2,5-dimethoxy-tetrahydro-furan-3-yl)pyridine (101 mg, 0.482 mmol), pyridine (156 μL, 1.92 mmol), and chlorotrimethylsilane (366 μL, 2.88 mmol) in 1,2-dichloroethane (5 mL) was heated at 90° C. After 3 days, the mixture was allowed to cool and concentrated in vacuo to give a brown oil which was purified via flash column chromatography with 0.5% HOAc/10% MeOH/CH2Cl2 as eluant to afford 90 mg (43%) of N-(2,2-dimethyl-1(S)-methylcarbamoylpropyl)-3(R)-(3-pyridin-4-yl-1H-pyrrol-1-yl)succinamic acid benzyl ester as a pale yellow powder, mp 130-3° C. 1H NMR (CD3OD): ∂ 8.36 (bs, 2H), 7.98 (d, 2H, J=4.4 Hz), 7.51 (d, 2H, J=5.0 Hz), 7.48 (t, 1H, J=1.8 Hz), 6.93 (t, 1H, J=2.5 Hz), 6.61 (dd, 1H, J=1.7,3.0Hz), 5.34 (t, 1H, J=7.6 Hz), 5.10 (dd, 2H, J=2.5, 14.3 Hz), 4.16 (s, 1H), 3.14 (dd, 1H, J=7.8 Hz, 16.5 Hz), 2.60 (d, 3H, J=3.4 Hz), 0.92 (s, 9H). IR (KBr): 3314, 2965, 1734, 1648, 1604, 1543, 1400, 1167 cm−1. HRFABMS: Calcd for C27H32N4O4Cs (M+Cs+): 609.1478. Found: 609.1499. Anal: Calculated for C27H32N4O4•0.1 CH2Cl2•MeOH: C, 65.27; H, 7.06; N, 10.83. Found: C, 65.52; H, 6.89; N, 10.52.

Workup

  1. temperatureto cool
  2. concentrationconcentrated in vacuo
  3. customto give a brown oil which
  4. customwas purified via flash column chromatography with 0.5% HOAc/10% MeOH/CH2Cl2 as eluant

Sources & evidence

ORD record
ord-d2efecc5cf1f44f984db461b54e0e32e
Source dataset
uspto-grants-2001_01
Patent number
US06174915B1

Reaction notes

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