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 566791노트

반응식

HRID 566791 반응식
[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]

참가 물질

5

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-989df8115bb04b829c7d604030c3fc44
출처 데이터셋
uspto-grants-2001_01
특허 번호
US06174915B1

반응 노트

불러오는 중…