Hydrochloric Acid → HCID 90016118, compound

HRID 920185Notes

Reaction equation

HRID 920185 reaction equation
COC1C=CC(C(C2C=CC(OC)=CC=2)(C2C=CC=CC=2)[NH:10][C:11]2[CH2:12][S:13][CH2:14][C@:15]([C:18]3[CH:23]=[C:22]([N:24]=C(C4C=CC=CC=4)C4C=CC=CC=4)[CH:21]=[CH:20][C:19]=3[F:38])([CH3:17])[N:16]=2)=CC=1.C(O)(C(F)(F)F)=O.Cl.[OH-].[NH4+]>ClCCl.CO.O1CCOCC1>[NH3:10].[NH2:24][C:22]1[CH:21]=[CH:20][C:19]([F:38])=[C:18]([C@:15]2([CH3:17])[CH2:14][S:13][CH2:12][C:11]([NH2:10])=[N:16]2)[CH:23]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 14923Ammonium HydroxideHCID 90025426HCID 90025426, compound

Product 2

HCID 222AmmoniaHCID 90016118HCID 90016118, compoundYield 55.7%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
23 °C

Procedure

To a solution of (R)—N-(bis(4-methoxyphenyl)(phenyl)methyl)-5-(5-(diphenylmethyleneamino)-2-fluorophenyl)-5-methyl-5,6-dihydro-2H-1,4-thiazin-3-amine (1.59 g, 2.25 mmol, Eq: 1.00) in dichloromethane (80 ml) at 23° C. was dropwise added TFA (12.8 g, 8.68 ml, 113 mmol, Eq: 50) and the resulting red solution was stirred at 23° C. for 3 hours, then dioxane (80 ml) was added followed by 1 M hydrochloric acid (2.25 ml, 2.25 mmol, Eq: 1.00) and stirring was continued at 23° C. for 2 hours. Poured into 25% ammonium hydroxide solution and extracted twice with dichloromethane, the combined organic layer was dried over Na2SO4, filtered off and evaporated totally. The crude material was purified by silica gel column chromatography first with ethyl acetate to remove all non-polar byproducts, then with 7 M ammonia in methanol to obtain the (R)-5-(5-amino-2-fluorophenyl)-5-methyl-5,6-dihydro-2H-1,4-thiazin-3-amine (150 mg, 627 μmol, 27.8% yield) as a light brown solid. MS (ISP): m/z=240.1 [M+H]+.

Workup

  1. customat 23° C.
  2. stirringstirring
  3. waitwas continued at 23° C. for 2 hours
  4. extractionextracted twice with dichloromethane
  5. dry with materialthe combined organic layer was dried over Na2SO4
  6. filtrationfiltered off
  7. customevaporated totally
  8. customThe crude material was purified by silica gel column chromatography first with ethyl acetate
  9. customto remove all non-polar byproducts

Sources & evidence

ORD record
ord-616194543a4e4fdd95d8acd02fd607e3
Source dataset
uspto-grants-2016_03
Patent number
US09273042B2

Reaction notes

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