Phosphate → N1-[2,2-Dimethyl-1(S)-(hydroxymethyl)propyl]-N4-hydroxy-2(R)-[3-[4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinamide

HRID 613898Notes

Reaction equation

HRID 613898 reaction equation
[O:1]([NH:19][C:20](=[O:50])[CH2:21][C@@H:22]([N:33]1[CH:37]=[CH:36][C:35]([C:38]2[CH:43]=[CH:42][C:41]([C:44]3[CH:49]=[CH:48][N:47]=[CH:46][CH:45]=3)=[CH:40][CH:39]=2)=[CH:34]1)[C:23]([NH:25][C@H:26]([CH2:31][OH:32])[C:27]([CH3:30])([CH3:29])[CH3:28])=[O:24])[Si](C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.P([O-])([O-])([O-])=O>C1COCC1>[CH3:28][C:27]([CH3:30])([CH3:29])[C@H:26]([NH:25][C:23](=[O:24])[C@H:22]([N:33]1[CH:37]=[CH:36][C:35]([C:38]2[CH:43]=[CH:42][C:41]([C:44]3[CH:49]=[CH:48][N:47]=[CH:46][CH:45]=3)=[CH:40][CH:39]=2)=[CH:34]1)[CH2:21][C:20]([NH:19][OH:1])=[O:50])[CH2:31][OH:32]

Participants

5

Reactant 3

HCID 1061PhosphateHCID 2724141Tetrabutylammonium FluorideHCID 59932758N4-t-butyldiphenylsiloxy-N1-[2,2-Dimethyl-1(S)-(hydroxymethyl)propyl]-2(R)-[3-[4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinamide

Product 1

HCID 9911606N1-[2,2-Dimethyl-1(S)-(hydroxymethyl)propyl]-N4-hydroxy-2(R)-[3-[4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinamideYield 42%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N4 -t-butyldiphenylsiloxy-N1 -[2,2-Dimethyl-1(S)-(hydroxymethyl)propyl]-2(R)-[3-[4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinamide (112 mg, 0.160 mmol) in THF (5 mL) was added a solution of tetra-n-butylammonium fluoride (0.20 mL of 1M in THF). After 1.25 hours at ambient temperature, the mixture was added dropwise to 1M pH7 phosphate buffer (40 mL). The resultant precipitate was collected by filtration and washed with H2O. A solution in CH2Cl2 /MeOH was passed through a 0.45μ syringe filter, and the filtrate was concentrated to give a solid which was triturated with EtOH to yield 30 mg (42%) of N1 -[2,2-Dimethyl-1(S)-(hydroxymethyl)propyl]-N4 -hydroxy-2(R)-[3-[4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinamide as an amorphous solid, which decomposed >200° C. 1H NMR (CD3COOD): δ 8.91 (d, 2H, J=6.6 Hz), 8.23 (d, 2H, J=7.0 Hz), 7.93 (d, 2H, J=8.8 Hz), 7.76 (d, 2H, J=8.5 Hz), 7.42 (s, 1H), 6.95 (s, 1h), 6.60 (s, 1H), 5.44 (t, 1H, J=7.4 Hz), 3.92-3.88 (m, 2H), 3.63-3.55 (m, 1H), 3.21 (dd, 1H, J=6.4, 14.5 Hz), 3.03 (dd, 1H, J=8.1, 15.1 Hz), 0.93 (s, 9H). Anal: Calculated for C25H30N4O4.0.4 H2O: C, 66.08; H, 6.96; N, 11.95. Found: C, 65.92; H, 6.79; N, 11.86.

Workup

  1. filtrationThe resultant precipitate was collected by filtration
  2. washwashed with H2O
  3. filtrationfilter
  4. concentrationthe filtrate was concentrated
  5. customto give a solid which
  6. customwas triturated with EtOH

Sources & evidence

ORD record
ord-02b95e845503411cb39395e9a134dfba
Source dataset
uspto-grants-1999_12
Patent number
US06008243

Reaction notes

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