Dichloromethane → HCID 68006008, compound

HRID 1026570Notes

Reaction equation

HRID 1026570 reaction equation
[Si:1]([O:18][CH2:19][CH2:20][C@H:21]([O:23][C:24]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=1[C:31]1[CH:36]=[CH:35][C:34]([C:37](O)=[O:38])=[C:33]([F:40])[CH:32]=1)[CH3:22])([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:41][C:42]1([CH3:86])[O:47][C:46]2[N:48]=[CH:49][C:50](C(F)(F)F)=[CH:51][C:45]=2[N:44]([CH:56]2[CH2:61][CH2:60][N:59](C(C3C=CC(C4C=CC=CC=4OCC(C)(C)C(O)=O)=CC=3F)=O)[CH2:58][CH2:57]2)[C:43]1=[O:85].C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[Cl:120]CCl>>[Si:1]([O:18][CH2:19][CH2:20][C@H:21]([O:23][C:24]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=1[C:31]1[CH:36]=[CH:35][C:34]([C:37]([N:59]2[CH2:60][CH2:61][CH:56]([N:44]3[C:43](=[O:85])[C:42]([CH3:86])([CH3:41])[O:47][C:46]4[N:48]=[CH:49][C:50]([Cl:120])=[CH:51][C:45]3=4)[CH2:57][CH2:58]2)=[O:38])=[C:33]([F:40])[CH:32]=1)[CH3:22])([C:14]([CH3:15])([CH3:16])[CH3:17])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 5

HCID 6344Dichloromethane2×HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68005439HCID 68005439, compoundHCID 68005845HCID 68005845, compound

Product 1

HCID 68006008HCID 68006008, compound

Procedure

At room temperature, to a dichloromethane solution (10 ml) of 2′-{[(1R)-3-{[tert-butyl(diphenyl)silyl]oxy}-1-methylpropyl]oxy}-3,5′-difluorobiphenyl-4-carboxylic acid (180 mg) were added 7-chloro-3,3-dimethyl-1-piperidin-4-yl-1H-pyrido[2,3-b][1,4]oxazin-2(3H)-one trifluoroacetate (Reference Example 3) (132 mg), diisopropylethylamine (0.280 ml) and 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (183 mg), followed by stirring overnight. The reaction solution was diluted with dichloromethane, washed sequentially with a 10% aqueous citric acid solution, a saturated aqueous sodium hydrogen carbonate solution and saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to afford 1-{1-[(2′-{[(1R)-3-{[tert-butyl(diphenyl)silyl]oxy}-1-methylpropyl]oxy}-3,5′-difluorobiphenyl-4-yl)carbonyl]piperidin-4-yl}-7-chloro-3,3-dimethyl-1H-pyrido[2,3-b][1,4]oxazin-2(3H)-one (256 mg).

Workup

  1. washwashed sequentially with a 10% aqueous citric acid solution
  2. dry with materiala saturated aqueous sodium hydrogen carbonate solution and saturated sodium chloride solution, dried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-b3a6168cb8c34570aa688ba9fa72a00f
Source dataset
uspto-grants-2014_05
Patent number
US08729095B2

Reaction notes

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