4-Methylmorpholine → HCID 86603059, compound

HRID 855355Notes

Reaction equation

HRID 855355 reaction equation
CN1CCOCC1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[Cl:30][C:31]1[CH:32]=[C:33]2[C:37](=[C:38]([C:41]([OH:43])=O)[C:39]=1[F:40])[NH:36][CH:35]=[CH:34]2.[F:44][C:45]([F:68])([F:67])[C:46]1[CH:47]=[C:48]([CH2:52][CH2:53][NH:54][CH2:55][C:56]2[CH:61]=[CH:60][C:59]([C:62]3([C:65]#[N:66])[CH2:64][CH2:63]3)=[CH:58][CH:57]=2)[CH:49]=[CH:50][CH:51]=1>CN(C=O)C.O>[C:65]([C:62]1([C:59]2[CH:58]=[CH:57][C:56]([CH2:55][N:54]([CH2:53][CH2:52][C:48]3[CH:49]=[CH:50][CH:51]=[C:46]([C:45]([F:67])([F:68])[F:44])[CH:47]=3)[C:41]([C:38]3[C:39]([F:40])=[C:31]([Cl:30])[CH:32]=[C:33]4[C:37]=3[NH:36][CH:35]=[CH:34]4)=[O:43])=[CH:61][CH:60]=2)[CH2:64][CH2:63]1)#[N:66]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 251136475-chloro-6-fluoro-1H-indole-7-carboxylic acidHCID 693424741-(4-{[2-(3-Trifluoromethyl-phenyl)-ethylamino]-methyl}-phenyl)-cyclopropanecarbonitrile

Product 1

HCID 86603059HCID 86603059, compoundYield 87%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

69 mg (0.7 mmol) of N-methyl morpholine and then 129 mg (0.34 mmol) of TBTU were added to 48 mg (0.23 mol) of 5-chloro-6-fluoro-1H-indol-7-carboxylic acid and 78 mg (0.27 mmol) of 1-(4-{[2-(3-trifluoromethyl-phenyl)-ethylamino]-methyl}-phenyl)-cyclo-propanecarbonitrile dissolved in 2.3 ml DMF at rt under nitrogen. The reaction mixture was stirred at rt over night. Water was added and the reaction mixture was extracted twice with EtOAc. The combined organic layers were washed once with 1N aqueous HCl solution, once with saturated aqueous NaHCO3 solution and once with saturated aqueous NaCl solution, dried over sodium sulfate, filtered and the solvent was evaporated. The residue was purified by column chromatography (20 g silica gel; methylene chloride/methanol 19:1) to yield 107 mg (87%) product as a yellow viscous oil. MS (ISP) 540.3 (100), 541.3 (30), 542.3 (32) (M+H)+, 562.3 (39), 563.4 (11), 564.4 (12) (M+Na)+.

Workup

  1. extractionthe reaction mixture was extracted twice with EtOAc
  2. washThe combined organic layers were washed once with 1N aqueous HCl solution, once with saturated aqueous NaHCO3 solution and once with saturated aqueous NaCl solution
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customthe solvent was evaporated
  6. customThe residue was purified by column chromatography (20 g silica gel; methylene chloride/methanol 19:1)

Sources & evidence

ORD record
ord-f95cc2dc846946608b9cad146828b1a8
Source dataset
uspto-grants-2007_08
Patent number
US07259183B2

Reaction notes

Loading…