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 566791ノート

反応式

HRID 566791 の反応式
[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]

参加物

5

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

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=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.

後処理

  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

出典と根拠

ORDレコード
ord-989df8115bb04b829c7d604030c3fc44
出典データセット
uspto-grants-2001_01
特許番号
US06174915B1

反応ノート

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