Hydrochloric Acid → Benzoic acid, 2,4-dimethyl-, [4-[(1R)-1-(aminomethyl)-2-(6-isoquinolinylamino)-2-oxoethyl]phenyl]methyl ester, hydrochloride (1:2)

HRID 1020107Notes

Reaction equation

HRID 1020107 reaction equation
[CH3:1][C:2]1[CH:40]=[C:39]([CH3:41])[CH:38]=[CH:37][C:3]=1[C:4]([O:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C@@H:14]([CH2:28][NH:29]C(OC(C)(C)C)=O)[C:15]([NH:17][C:18]2[CH:19]=[C:20]3[C:25](=[CH:26][CH:27]=2)[CH:24]=[N:23][CH:22]=[CH:21]3)=[O:16])=[CH:10][CH:9]=1)=[O:5].[ClH:42]>C(Cl)Cl>[ClH:42].[ClH:42].[CH3:1][C:2]1[CH:40]=[C:39]([CH3:41])[CH:38]=[CH:37][C:3]=1[C:4]([O:6][CH2:7][C:8]1[CH:9]=[CH:10][C:11]([C@H:14]([CH2:28][NH2:29])[C:15]([NH:17][C:18]2[CH:19]=[C:20]3[C:25](=[CH:26][CH:27]=2)[CH:24]=[N:23][CH:22]=[CH:21]3)=[O:16])=[CH:12][CH:13]=1)=[O:5]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 66613838(S)-4-(3-((tert-butoxycarbonyl)amino)-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl)benzyl 2,4-dimethylbenzoate

Product 1

HCID 66599965Benzoic acid, 2,4-dimethyl-, [4-[(1R)-1-(aminomethyl)-2-(6-isoquinolinylamino)-2-oxoethyl]phenyl]methyl ester, hydrochloride (1:2)

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(R)-4-(3-amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl)benzyl 2,4-dimethylbenzoate dihydrochloride (E197-R) was prepared from E145-R according to the scheme in FIG. 6. To (S)-4-(3-(tert-butoxycarbonylamino)-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl)benzyl 2,4-dimethylbenzoate (E145-R) in CH2Cl2 was added HCl (4 N in dioxane) and the solution was stirred for 8-10 h. The solvents were evaporated to give pure (R)-4-(3-amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl)benzyl 2,4-dimethylbenzoate dihydrochloride (E197-R). Analysis by chiral HPLC (Chiralpak AS-H, eluent: 90:10:0.1 EtOH:H2O:diethylamine) showed enantiomeric excess >98%.

Workup

  1. custom(R)-4-(3-amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl)benzyl 2,4-dimethylbenzoate dihydrochloride (E197-R) was prepared
  2. customThe solvents were evaporated

Sources & evidence

ORD record
ord-6a6f31590692414eba9f95ad6393d910
Source dataset
uspto-grants-2014_05
Patent number
US08716310B2

Reaction notes

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