Hydrochloric Acid → HCID 66894003, compound

HRID 1921231Notes

Reaction equation

HRID 1921231 reaction equation
C(OC([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]1[C:18]([OH:20])=[O:19])=O)(C)(C)C.[OH:21][NH:22][C:23](=[NH:25])[CH3:24].[ClH:26].[CH3:27]N(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.Cl.O1CCOCC1>>[ClH:26].[CH3:24][C:23]1[N:25]=[C:27]([C:9]2([C:18]([OH:20])=[O:19])[C:10]3[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=3)[CH2:16][CH2:17][NH:8]2)[O:21][N:22]=1

Participants

7

Reactant 6

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 152807232-(tert-Butoxycarbonyl)-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acidHCID 178465666HCID 178465666, compound

Product 1

HCID 66894003HCID 66894003, compound

Procedure

A solution of 2-(tert-butyoxycarbonyl)-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid (2.00 g, 7.21 mmol), N-hydroxyacetamidine (1.39 g, 18.8 mmol), [3-(dimethylamino)propyl]ethyl carbodiimide hydrochloride (3.04 g, 15.9 mmol), and 1-hydroxybenzotriazole (1.55 g, 1.01 mmol) was heated to 100° C. for 18 hours, then cooled to rt and concentrated in vacuo. The resultant residue was redissolved in ethyl acetate and washed with saturated aqueous sodium bicarbonate and brine, dried over sodium sulfate, filtered, concentrated in vacuo, and subjected to silica gel chromatography from 0 to 20% ethyl actate in hexanes. To a solution of the resultant compound (0.600 g, 1.90 mmol) was added 4 N HCl in dioxane (1.42 mL, 4.26 mmol). After 2 hours, the reaction was concentrated in vacuo to provide the title compound as a beige solid that gave a proton NMR spectrum consistent with theory and a mass ion (ES+) of 216.2. This crude intermediate was used to prepare Example 21, by the procedure described for Example 1.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe resultant residue was redissolved in ethyl acetate
  3. washwashed with saturated aqueous sodium bicarbonate and brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. concentrationthe reaction was concentrated in vacuo

Sources & evidence

ORD record
ord-377689efef6a4d06bdc6ab4224c10de7
Source dataset
uspto-grants-2012_05
Patent number
US08173672B2

Reaction notes

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