Diisopropylethylamine → tert-butyl 3-{[3'-fluoro-4'-({4-[(3S)-7-fluoro-3-methyl-2-oxo-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-1-yl]piperidin-1-yl}carbonyl)biphenyl-2-yl]oxy}-2,2-dimethylpropanoate

HRID 1026560Notes

Reaction equation

HRID 1026560 reaction equation
[F:1][C:2]1[CH:19]=[N:18][C:5]2[O:6][C@@H:7]([CH3:17])[C:8](=[O:16])[N:9]([CH:10]3[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]3)[C:4]=2[CH:3]=1.[C:20]([O:24][C:25](=[O:47])[C:26]([CH3:46])([CH3:45])[CH2:27][O:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[C:35]1[CH:40]=[CH:39][C:38]([C:41](O)=[O:42])=[C:37]([F:44])[CH:36]=1)([CH3:23])([CH3:22])[CH3:21].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>O.CN(C)C=O>[F:44][C:37]1[CH:36]=[C:35]([C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=2[O:28][CH2:27][C:26]([CH3:46])([CH3:45])[C:25]([O:24][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:47])[CH:40]=[CH:39][C:38]=1[C:41]([N:13]1[CH2:12][CH2:11][CH:10]([N:9]2[C:8](=[O:16])[C@H:7]([CH3:17])[O:6][C:5]3[N:18]=[CH:19][C:2]([F:1])=[CH:3][C:4]2=3)[CH2:15][CH2:14]1)=[O:42]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 680062602'-(3-Tert-butoxy-2,2-dimethyl-3-oxopropoxy)-3-fluorobiphenyl-4-carboxylic acidHCID 68006437(3S)-7-fluoro-3-methyl-1-piperidin-4-yl-1H-pyrido[2,3-b][1,4]oxazin-2(3H)-one

Product 1

HCID 68005985tert-butyl 3-{[3'-fluoro-4'-({4-[(3S)-7-fluoro-3-methyl-2-oxo-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-1-yl]piperidin-1-yl}carbonyl)biphenyl-2-yl]oxy}-2,2-dimethylpropanoateYield 90.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

At room temperature, to an N,N-dimethylformamide solution (10 ml) of (3S)-7-fluoro-3-methyl-1-piperidin-4-yl-1H-pyrido[2,3-b][1,4]oxazin-2(3H)-one (Reference Example 2) (434 mg) and 2′-(3-tert-butoxy-2,2-dimethyl-3-oxopropoxy)-3-fluorobiphenyl-4-carboxylic acid (636 mg) were added 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (683 mg) and diisopropylethylamine (0.855 ml), followed by stirring for 24 hours. The reaction solution was poured into water (40 ml), and stirred for 6 hours. The precipitate was collected by filtration and dried to afford tert-butyl 3-{[3′-fluoro-4′-({4-[(3S)-7-fluoro-3-methyl-2-oxo-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-1-yl]piperidin-1-yl}carbonyl)biphenyl-2-yl]oxy}-2,2-dimethylpropanoate (940 mg).

Workup

  1. stirringstirred for 6 hours
  2. filtrationThe precipitate was collected by filtration
  3. customdried

Sources & evidence

ORD record
ord-bb1f2ff31b4541c4bc2139a4442dd99e
Source dataset
uspto-grants-2014_05
Patent number
US08729095B2

Reaction notes

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