Hydrochloric Acid → HCID 178513998, compound

HRID 591927Notes

Reaction equation

HRID 591927 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[Cl:8][C:9]1[C:10]([NH:31][C@@H:32]2[C@@H:37]3[CH2:38][C@@H:34]([CH:35]=[CH:36]3)[C@@H:33]2[C:39]([NH2:41])=[O:40])=[C:11]2[N:17]=[C:16]([C:18]3[CH:23]=[CH:22][C:21](CN4CCOCC4)=[CH:20][CH:19]=3)[NH:15][C:12]2=[N:13][CH:14]=1.NC1[C:48]([NH2:49])=[C:47]([NH:50][C@@H:51]2[C@@H:56]3C[C@@H](C=C3)[C@@H]2C(N)=O)C(Cl)=CN=1.C(OC(N1CCN(C2C=CC(C=O)=CC=2)CC1)=O)(C)(C)C.C(=O)(OC(C)(C)C)N.Cl>O1CCOCC1>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[Cl:8][C:9]1[C:10]([NH:31][C@@H:32]2[C@@H:37]3[CH2:38][C@@H:34]([CH:35]=[CH:36]3)[C@@H:33]2[C:39]([NH2:41])=[O:40])=[C:11]2[N:17]=[C:16]([C:18]3[CH:19]=[CH:20][C:21]([N:49]4[CH2:48][CH2:47][NH:50][CH2:51][CH2:56]4)=[CH:22][CH:23]=3)[NH:15][C:12]2=[N:13][CH:14]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 77922tert-Butyl carbamateHCID 2795509Tert-butyl 4-(4-formylphenyl)piperazine-1-carboxylateHCID 117701912(1S,2S,3R,4R)-3-(2,3-Diamino-5-chloro-pyridin-4-ylamino)-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amideHCID 178513995HCID 178513995, compound

Product 1

HCID 178513998HCID 178513998, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

In the same fashion as for Compound III, (1S,2S,3R,4R)-3-(2,3-Diamino-5-chloro-pyridin-4-ylamino)-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide and 4-(4-Formyl-phenyl)-piperazine-1-carboxylic acid tert-butyl ester were reacted to produce an initial tert-butyl carbamate condensation product. This material was treated with 4N hydrochloric acid in dioxane at 40° C. overnight. Concentration followed by reverse phase chromatography on a Gilson chromatograph afforded fractions which were lyophilized to afford the title compound (43%). 1H NMR (d6-DMSO): 13.19 (br s, 1H), 8.77 (m, 2H), 8.04 (s, 1H), 8.02 (s, 1H), 7.95 (s, 1H), 7.78 (s, 1H), 7.13-7.45 (m, 4H), 6.38 (m, 2H), 5.17 (t, J=8 Hz, 1H), 3.49 (m, 4H), 3.26 (m, 4H), 2.91 (s, 1H), 2.80 (s, 1H), 2.62 (d, J=8 Hz, 1H), 2.23 (d, J=9 Hz, 1H), 1.40 (d, J=9 Hz, 1H). MS: 465.09 (M+H). HPLC retention time: 1.79 minutes (G Method).

Workup

  1. customto produce
  2. concentrationConcentration
  3. customafforded fractions which

Sources & evidence

ORD record
ord-31540eca63b4482e85a27b828be1a142
Source dataset
uspto-grants-2016_01
Patent number
US09238656B2

Reaction notes

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