Hydrochloric Acid → 1-Amino-6-[(2-(3-(cyclohexylmethylsulfonylamino)-6-methyl-2-oxo-1,2-dihydropyridinyl)-1-oxo-ethyl)aminomethyl]isoquinoline hydrochloride

HRID 2304307Notes

Reaction equation

HRID 2304307 reaction equation
[CH:1]1([CH2:7][S:8]([NH:11][C:12]2[C:13](=[O:23])[N:14]([CH2:19][C:20](O)=[O:21])[C:15]([CH3:18])=[CH:16][CH:17]=2)(=[O:10])=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:24][C:25]1[C:34]2[C:29](=[CH:30][C:31]([CH2:35][NH2:36])=[CH:32][CH:33]=2)[CH:28]=[CH:27][N:26]=1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.CN1CCOCC1.[ClH:66]>ClCCl.CN(C)C=O.C(O)(C)(C)C.O>[ClH:66].[NH2:24][C:25]1[C:34]2[C:29](=[CH:30][C:31]([CH2:35][NH:36][C:20](=[O:21])[CH2:19][N:14]3[C:15]([CH3:18])=[CH:16][CH:17]=[C:12]([NH:11][S:8]([CH2:7][CH:1]4[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]4)(=[O:9])=[O:10])[C:13]3=[O:23])=[CH:32][CH:33]=2)[CH:28]=[CH:27][N:26]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate2×HCID 221697756-(Aminomethyl)isoquinolin-1-amineHCID 57104637[3-(Cyclohexylmethylsulfonylamino)-6-methyl-2-oxo-1,2-dihydropyridinyl]-acetic acid

Product 1

HCID 697812311-Amino-6-[(2-(3-(cyclohexylmethylsulfonylamino)-6-methyl-2-oxo-1,2-dihydropyridinyl)-1-oxo-ethyl)aminomethyl]isoquinoline hydrochloride

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 714019492-Methylpropan-2-ol--water (1/1)Solvent

Procedure

To a stirred solution of 0.14 g of [3-(cyclohexylmethylsulfonylamino)-6-methyl-2-oxo-1,2-dihydropyridinyl]-acetic acid and 0.07 g of 1-amino-6-(aminomethyl)isoquinoline in 5 mL dichloromethane and 2 mL N,N-dimethylformamide was added 0.19 g 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU). After 16 h at room temperature additional 50 mg TBTU and 0.10 mL N-methylmorpholine were added and the mixture was stirred at room temperature for an additional 16 h. Dichloromethane was added and the reaction mixture was washed with aqueous saturated sodium hydrogencarbonate and water. Both aqueous washes were extracted three times with dichloromethane. The combined organic phases were dried over sodium sulphate and concentrated. The residue was purified by chromatography on silica gel (eluent: dichloromethane/methanol=9/1 v/v) to yield the free base. This free base was dissolved in a mixture of t-butanol/water=1/1 (v/v) and one equivalent hydrochloric acid was added. Lyophilisation yielded 135 mg of the title compound. MS ESI+: 498 (M+H).

Workup

  1. washthe reaction mixture was washed with aqueous saturated sodium hydrogencarbonate and water
  2. extractionBoth aqueous washes were extracted three times with dichloromethane
  3. dry with materialThe combined organic phases were dried over sodium sulphate
  4. concentrationconcentrated
  5. customThe residue was purified by chromatography on silica gel (eluent: dichloromethane/methanol=9/1 v/v)
  6. customto yield the free base
  7. additionwas added

Sources & evidence

ORD record
ord-8f73521a8b4e4f3eb6d6728b0b96ad2f
Source dataset
uspto-grants-2002_08
Patent number
US06432955B1

Reaction notes

Loading…