Water → 6-chloro-4'-{5-chloro-2-[1-ethyl-1-((S)-2,3-dihydroxy-propylcarbamoyl)-propoxy]-phenyl}-2'-(5-fluoro-2-methyl-phenyl)spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

HRID 504562Notes

Reaction equation

HRID 504562 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:41])[C:10]3([CH:15]([C:16]4(CC)[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][CH:17]4[O:23][CH:24]([C:27]([OH:29])=O)[CH2:25][CH3:26])[CH2:14][C:13](=[O:32])[NH:12][CH:11]3[C:33]3[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:34]=3[CH3:40])[C:5]2=[CH:4][CH:3]=1.[NH2:42][CH2:43][C@H:44]([OH:47])[CH2:45][OH:46].CN(C(ON1N=N[C:58]2C=CC=N[C:57]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.O>CN(C1C=CN=CC=1)C.CN(C=O)C>[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:41])[C:10]3([CH:15]([C:16]4[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:17]=4[O:23][C:24]([CH2:25][CH3:26])([C:27](=[O:29])[NH:42][CH2:43][C@H:44]([OH:47])[CH2:45][OH:46])[CH2:57][CH3:58])[CH2:14][C:13](=[O:32])[NH:12][CH:11]3[C:33]3[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:34]=3[CH3:40])[C:5]2=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 4409023-Amino-1,2-propanediol, (S)-HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 775026446-chloro-4'-[1-ethyl-5-chloro-2-(1-hydroxycarbonyl-propoxy)-phenyl]-2'-(5-fluoro-2-methyl-phenyl)spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

Product 1

HCID 866320906-chloro-4'-{5-chloro-2-[1-ethyl-1-((S)-2,3-dihydroxy-propylcarbamoyl)-propoxy]-phenyl}-2'-(5-fluoro-2-methyl-phenyl)spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dioneYield 70.8%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

At room temperature, a mixture of racemic (2′S,3S,4′R)-6-chloro-4′-[1-ethyl-5-chloro-2-(1-hydroxycarbonyl-propoxy)-phenyl]-2′-(5-fluoro-2-methyl-phenyl)spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione (50 mg, 0.084 mmol), (S)-3-amino-1,2-propanediol (27 mg, 0.3 mmol), HATU (114 mg, 0.30 mmol) and DMAP (72 mg, 0.59 mmol) in DMF (2 mL) was stirred for 5 h. Then the mixture was poured into water and extracted with EtOAc thrice. The combined organic phase was washed with saturated NaCl solution twice, dried over anhydrous Na2SO4 and concentrated. The residue was purified by flash column to give the title compound as a white solid (40 mg).

Workup

  1. extractionextracted with EtOAc thrice
  2. washThe combined organic phase was washed with saturated NaCl solution twice
  3. dry with materialdried over anhydrous Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by flash column

Sources & evidence

ORD record
ord-8fb31fd4303043409509471167f1e95d
Source dataset
uspto-grants-2010_08
Patent number
US07776875B2

Reaction notes

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