Hydrochloric Acid → HCID 86689159, compound

HRID 1752473Notes

Reaction equation

HRID 1752473 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([C@:8]2([CH3:40])[C:13]([F:15])([F:14])[CH2:12][O:11][C:10]([NH:16][C:17]([C:32]3[CH:37]=[CH:36][C:35](OC)=[CH:34][CH:33]=3)([C:24]3[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=3)[C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[N:9]2)[C:5]([F:41])=[CH:4][CH:3]=1.[Cl:42][C:43]1[C:44]([C:53]([OH:55])=O)=[N:45][CH:46]=[C:47]([C:49]([F:52])([F:51])[F:50])[CH:48]=1.C1C=NC2N(O)N=NC=2C=1.Cl.CN([CH:70]=[O:71])C>C(OCC)(=O)C.C(Cl)CCl>[F:15][C:13]1([F:14])[CH2:12][O:11][C:10]([NH:16][C:17]([C:24]2[CH:25]=[CH:26][C:27]([O:30][CH3:31])=[CH:28][CH:29]=2)([C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([O:71][CH3:70])[CH:33]=2)[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)=[N:9][C@@:8]1([C:6]1[N:7]=[C:2]([NH:1][C:53]([C:44]2[C:43]([Cl:42])=[CH:48][C:47]([C:49]([F:50])([F:51])[F:52])=[CH:46][N:45]=2)=[O:55])[CH:3]=[CH:4][C:5]=1[F:41])[CH3:40]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 181649HOAtHCID 28219083-Chloro-5-(trifluoromethyl)pyridine-2-carboxylic acidHCID 86689158HCID 86689158, compound

Product 1

HCID 86689159HCID 86689159, compoundYield 29.2%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

[(R)-4-(6-amino-3-fluoro-pyridin-2-yl)-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-yl]-[bis-(4-methoxy-phenyl)-phenyl-methyl]-amine (250 mg, 0.444 mmol), 3-chloro-5-(trifluoromethyl)-picolinic acid (120 mg, 0.533 mmol) and HOAt (109 mg, 0.800 mmol) were dissolved in DMF (4.44 ml) under argon. EDC×HCl (128 mg, 0.667 mmol) was added and the reaction mixture was stirred at it for 18 hours. The reaction mixture was diluted with ethyl acetate, washed with water and brine, dried over sodium sulfate, filtered and concentrated. The crude product was chromatographed over silica gel (Redisep column 12 g, cyclohexane/ethyl acetate) to give the title compound: 100 mg (29.2% yield).

Workup

  1. washwashed with water and brine
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product was chromatographed over silica gel (Redisep column 12 g, cyclohexane/ethyl acetate)

Sources & evidence

ORD record
ord-d59e1d10047a4008834d0cc4b8c58bcf
Source dataset
uspto-grants-2015_10
Patent number
US09163011B2

Reaction notes

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