HCID 53789083, compound → HCID 59932748, compound

HRID 566764Notes

Reaction equation

HRID 566764 reaction equation
[C:1]1([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH:6]=[CH:5][C:4]([C:7]2[CH:11]=[CH:10][N:9]([C@@H:12]([C:17]([NH:19][C@H:20]([C:25](=[O:30])N(OC)C)[CH2:21][CH:22]([CH3:24])[CH3:23])=[O:18])[CH2:13][C:14]([OH:16])=[O:15])[CH:8]=2)=[CH:3][CH:2]=1.[CH3:37][Mg]Br>C1COCC1>[C:25]([C@@H:20]([NH:19][C:17](=[O:18])[C@H:12]([N:9]1[CH:10]=[CH:11][C:7]([C:4]2[CH:5]=[CH:6][C:1]([C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=3)=[CH:2][CH:3]=2)=[CH:8]1)[CH2:13][C:14]([OH:16])=[O:15])[CH2:21][CH:22]([CH3:24])[CH3:23])(=[O:30])[CH3:37]

Participants

4

Reactant 2

HCID 53789083HCID 53789083, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 59932748HCID 59932748, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3(R)-(3-biphenyl-4-yl-1H-pyrrol-1-yl)-N-[1(S)-(N-methoxy-N-methylcarbamoyl)-3-methyl-butyl]succinamic acid (prepared as described in Example 1(l); 209 mg, 0.425 mmol) in THF (5mL) at −78° C. was added methylmagnesium bromide (3 M in ether, 0.7mL) dropwise via syringe. After 15 minutes at −70° C. and 2 hours at 0° C., the mixture was quenched with acetone (50 μL), and then added to EtOAc/1N NaHSO4. The aqueousueous phase was extracted with EtOAc. The combined organic layers were dried over Na2SO4 and concentrated. After 3 days at ambient temperature, the dark residue began to crystallize, and trituration with MTBE/hexanes provided 90 mg (46%) of pure N-(1(S)-acetyl-3-methylbutyl)-3(R)-[3-(biphenyl-4-yl)-1H-pyrrol-1-yl)succinamic acid as an off-white solid. 1H NMR (CDCl3): δ 7.62-7.55 (m, 6H), 7.44 (t, 2H, J=7.5 Hz), 7.33 (t, 1H, J=7.0 Hz), 7.11 (s, 1H), 6.81 (t, 1H, J=2.4 Hz), 6.62 (dd, 1H, J=1.3, 2.4 Hz), 6.07 (d, 1H, J=8.5 Hz), 5.12 (t, 1H, J=6.8 Hz), 4.61-4.54 (m, 1H), 3.46 (dd, 1H, J=6.4, 16.7 Hz), 3.01 (dd, 1H, J=7.4, 16.9 Hz), 2.16 (s, 3H), 1.58-1.51 (m, 2H), 1.33 (d, 1H, J=7.4 Hz), 0.92 (d, 3H, J=6.3 Hz), 0.87 (d, 3H, J=6.3 Hz). Anal. Calculated for C27H30N2O4•0.5 H2O: C, 71.18; H, 6.86; N, 6.15. Found: C, 71.01; H, 6.78; N, 6.40.

Workup

  1. custom2 hours at 0° C., the mixture was quenched with acetone (50 μL)
  2. additionadded to EtOAc/1N NaHSO4
  3. extractionThe aqueousueous phase was extracted with EtOAc
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. concentrationconcentrated
  6. waitAfter 3 days at ambient temperature
  7. customto crystallize

Sources & evidence

ORD record
ord-3cd01cfc429e4870a00cdae5a886abc9
Source dataset
uspto-grants-2001_01
Patent number
US06174915B1

Reaction notes

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