Triethylamine → Hydrochloric Acid

HRID 1816051Notes

Reaction equation

HRID 1816051 reaction equation
C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[Cl:25][C:26]1[CH:34]=[CH:33][C:32]([CH2:35][CH2:36][CH2:37][N:38](C(OC(C)(C)C)=O)[CH2:39][CH2:40][NH:41][CH2:42]C(OC(C)(C)C)=O)=[CH:31][C:27]=1[C:28]([OH:30])=O.[C:57]12([CH2:67][NH2:68])[CH2:66][CH:61]3[CH2:62][CH:63]([CH2:65][CH:59]([CH2:60]3)[CH2:58]1)[CH2:64]2.C(N(CC)CC)C>CN(C)C=O.C(OCC)(=O)C>[ClH:25].[ClH:25].[ClH:25].[Cl:25][C:26]1[CH:34]=[CH:33][C:32]([CH2:35][CH2:36][CH2:37][NH:38][CH2:39][CH2:40][NH:41][CH3:42])=[CH:31][C:27]=1[C:28]([NH:68][CH2:67][C:57]12[CH2:66][CH:61]3[CH2:60][CH:59]([CH2:65][CH:63]([CH2:62]3)[CH2:64]1)[CH2:58]2)=[O:30]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 86625Tricyclo(3.3.1.13,7)dec-1-ylmethylamineHCID 2733179PyBroPHCID 21900018HCID 21900018, compound

Product 2

HCID 313Hydrochloric AcidHCID 131724839HCID 131724839, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

PyBrOP (0.2 g) was added to a solution of 2-chloro-5-[3-[[(1,1-dimethylethoxy)carbonyl][2-[[(1,1-dimethylethoxy)carbonyl]methylamino]ethyl]-amino]propyl]-benzoic acid (0.2 g, Example 13b), adamantanemethylamine (0. 1 ml) and triethylamine (0.15 ml) in N,N-dimethylformamide (10 ml). After 1 h the reaction mixture was diluted with ethyl acetate and washed with water, then washed twice with ammonium is chloride solution, twice with saturated sodium hydrogencarbonate solution and once with brine. The organic extracts were dried over magnesium sulfate, filtered, evaporated and purified by chromatography on silica (eluting with dichloromethane: methanol/2-10%). The product was redissolved in dichloromethane: methanol/1:1 (15 ml) and 4M hydrochloric acid in dioxane (2 ml) added. The mixture was stirred until deprotection was complete then purified by prep RP-HPLC (acetonitrile/0.1% aqueous trifluoroacetic acid). Conversion to the hydrochloride salt by treatment with 4M hydrochloric acid in 1,4-dioxane/methanol gave the title compound (0.055 g).

Workup

  1. washwashed with water
  2. washwashed twice with ammonium
  3. dry with materialThe organic extracts were dried over magnesium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. custompurified by chromatography on silica (eluting with dichloromethane: methanol/2-10%)
  7. dissolutionThe product was redissolved in dichloromethane
  8. additionmethanol/1:1 (15 ml) and 4M hydrochloric acid in dioxane (2 ml) added
  9. customwas complete then purified by prep RP-HPLC (acetonitrile/0.1% aqueous trifluoroacetic acid)

Sources & evidence

ORD record
ord-d50ffde6b5eb47389cb7e7861ecba8ca
Source dataset
uspto-grants-2005_04
Patent number
US06881754B2

Reaction notes

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