Hydrochloric Acid → HCID 10143150, compound

HRID 2414826Notes

Reaction equation

HRID 2414826 reaction equation
C(O[C:6](=[O:32])[NH:7][CH2:8][CH2:9][N:10]1[CH2:19][CH2:18][C:17]2[C:12](=[CH:13][C:14]([O:22][CH3:23])=[C:15]([O:20][CH3:21])[CH:16]=2)[CH:11]1[CH2:24][C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=1)(C)(C)C.Cl.C1N=CN(C(N2C=NC=C2)=O)C=1.[NH2:46][C:47]1[C:56]2[C:51](=[N:52][C:53]([CH3:57])=[CH:54][CH:55]=2)[N:50]=[CH:49][CH:48]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>CC(O)=O.O>[F:31][C:28]1[CH:29]=[CH:30][C:25]([CH2:24][CH:11]2[C:12]3[C:17](=[CH:16][C:15]([O:20][CH3:21])=[C:14]([O:22][CH3:23])[CH:13]=3)[CH2:18][CH2:19][N:10]2[CH2:9][CH2:8][NH:7][C:6]([NH:46][C:47]2[C:56]3[C:51](=[N:52][C:53]([CH3:57])=[CH:54][CH:55]=3)[N:50]=[CH:49][CH:48]=2)=[O:32])=[CH:26][CH:27]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 2724254Sodium bis(trimethylsilyl)amideHCID 124552017-Methyl-[1,8]naphthyridin-4-ylamineHCID 69763736{2-[1-(4-fluoro-benzyl)-6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl]-ethyl}-carbamic acid tert-butyl ester

Product 1

HCID 10143150HCID 10143150, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Procedure

To a stirred solution of {2-[1-(4-fluoro-benzyl)-6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl]-ethyl}-carbamic acid tert-butyl ester (example 106.1, 0.22 g, 0.5 mmol) in glacial AcOH (1 mL) is added conc. HCl (0.1 mL). After 5 min, the reaction mixture is partitioned with CHCl3 (20 mL) and 1 N NaOH (15 mL). The organic phase is evaporated. The residue is taken up in DMSO (2 mL) and treated with CDI (0.2 g, 0.6 mmol, 1.2 eq). The reaction mixture is stirred at rt for 3 h, and then 4-amino-7-methyl-[1,8]-naphthyridine (example C5, 0.19 g, 0.6 mmol) is added. To the resulting solution is added in a single portion NaHMDS (2 M in THF, 1.25 mL, 2.5 mmol). The reaction mixture is stirred at rt for 30 min, then H2O (0.4 mL) is added. The reaction mixture is evaporated and the residue purified by preparative HPLC to provide the title compound.

Workup

  1. customthe reaction mixture is partitioned with CHCl3 (20 mL) and 1 N NaOH (15 mL)
  2. customThe organic phase is evaporated
  3. stirringThe reaction mixture is stirred at rt for 30 min
  4. customThe reaction mixture is evaporated
  5. customthe residue purified by preparative HPLC

Sources & evidence

ORD record
ord-0ff791c0f9cb4120988598d97de24975
Source dataset
uspto-grants-2004_11
Patent number
US06815451B2

Reaction notes

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