Potassium Carbonate → (3-{(S)-5-[5-Chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-indan-1-ylcarbamoyl}-oxetan-3-yl)-carbamic acid 9H-fluoren-9-ylmethyl ester

HRID 2046560Notes

Reaction equation

HRID 2046560 reaction equation
[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C:19]3([C:23](O)=[O:24])[CH2:22][O:21][CH2:20]3)=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.[Cl:49][C:50]1[CH:51]=[C:52]([F:72])[C:53]([C:66]2[N:70]=[C:69]([CH3:71])[O:68][N:67]=2)=[C:54]([C:56]2[CH:57]=[C:58]3[C:62](=[CH:63][CH:64]=2)[C@@H:61]([NH2:65])[CH2:60][CH2:59]3)[CH:55]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.O>[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16](=[O:17])[NH:18][C:19]3([C:23](=[O:24])[NH:65][C@@H:61]4[C:62]5[C:58](=[CH:57][C:56]([C:54]6[CH:55]=[C:50]([Cl:49])[CH:51]=[C:52]([F:72])[C:53]=6[C:66]6[N:70]=[C:69]([CH3:71])[O:68][N:67]=6)=[CH:64][CH:63]=5)[CH2:59][CH2:60]4)[CH2:22][O:21][CH2:20]3)[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1

Participants

8

Reactant 5

HCID 11430Potassium CarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 679511683-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)oxetane-3-carboxylic acidHCID 68296736(S)-5-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-indan-1-ylamine

Product 1

HCID 68296802(3-{(S)-5-[5-Chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-indan-1-ylcarbamoyl}-oxetan-3-yl)-carbamic acid 9H-fluoren-9-ylmethyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 3-(9H-fluoren-9-ylmethoxycarbonylamino)-oxetane-3-carboxylic acid (1.70 g, 5.01 mmol) in dry DMF (50.0 ml) were added N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (1.60 g, 8.35 mmol) and 1-hydroxybenzotriazole hydrate (0.95 g, 6.20 mmol) at room temperature. The resulting colorless solution was stirred for 10 min before a solution of (S)-5-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-indan-1-ylamine (1.64 g, 4.77 mmol, intermediate A-11) in dry DMF (2.0 ml) was added. This mixture was stirred at room temperature for 20 h. Then water was added, the pH was adjusted to 9 with sat. K2CO3 solution and the mixture was extracted twice with MeCl2. The combined organic layers were washed with water and brine, dried with MgSO4 and evaporated. The remaining light brown foam was purified by chromatography (silica gel; MeCl2/MeOH 100:0 to 98:2%) and the title compound was obtained as off white foam (3.17 g, 100%). MS: 665.2 (MH+, 1Cl).

Workup

  1. additionwas added
  2. extractionthe mixture was extracted twice with MeCl2
  3. washThe combined organic layers were washed with water and brine
  4. dry with materialdried with MgSO4
  5. customevaporated
  6. customThe remaining light brown foam was purified by chromatography (silica gel; MeCl2/MeOH 100:0 to 98:2%)

Sources & evidence

ORD record
ord-93dc9868eda341a28ede523e866941ba
Source dataset
uspto-grants-2013_11
Patent number
US08592426B2

Reaction notes

Loading…