HCID 86663634, compound → Valbenazine

HRID 1807443Notes

Reaction equation

HRID 1807443 reaction equation
[CH2:1]([C@@H:5]1[CH2:22][N:9]2[CH2:10][CH2:11][C:12]3[C:17]([C@H:8]2[CH2:7][C@H:6]1[O:23][C:24](=[O:40])[CH:25]([NH:29]C(OCC1C=CC=CC=1)=O)[CH:26]([CH3:28])[CH3:27])=[CH:16][C:15]([O:18][CH3:19])=[C:14]([O:20][CH3:21])[CH:13]=3)[CH:2]([CH3:4])[CH3:3]>CO.[Pd]>[CH2:1]([C@@H:5]1[CH2:22][N:9]2[CH2:10][CH2:11][C:12]3[C:17]([C@H:8]2[CH2:7][C@H:6]1[O:23][C:24](=[O:40])[C@@H:25]([NH2:29])[CH:26]([CH3:28])[CH3:27])=[CH:16][C:15]([O:18][CH3:19])=[C:14]([O:20][CH3:21])[CH:13]=3)[CH:2]([CH3:4])[CH3:3]

Participants

4

Reactant 1

HCID 86663634HCID 86663634, compound

Product 1

HCID 24795069ValbenazineYield 86.2%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

1 (200 mg, 0.63 mmol) was dissolved in 3 mL anhydrous CH2Cl2 and DMAP (75.0 mg, 0.63 mmol) and Cbz-L-valine (190 mg, 0.75 mmol) were added and the mixture stirred for 5 min. DCC (155 mg, 0.75 mmol) was added and a white precipitate formed immediately. The mixture was stirred overnight then filtered and concentrated. Purification via flash column chromatography (0.2:9.8, MeOH:CH2Cl2) gave 360 mg (0.63 mmol) of 2-benzyloxycarbonylamino-3-methyl-butyric acid (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-yl ester 2a as a pale yellow solid in quantitative yield. Compound 2a (163 mg, 0.29 mmol) was dissolved in MeOH (10 mL) and Pd/C was added and the mixture was purged with H2. The mixture was stirred overnight, filtered through celite and concentrated. Purification via flash column chromatography (0.5:9.5, MeOH:CH2Cl2) gave 105 mg (0.25 mmol) of (S)-2-amino-3-methyl-butyric acid (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-yl ester 2-1 in 85% yield. MS calcd: (419). Found 419.3 (M+H).

Workup

  1. customthe mixture was purged with H2
  2. filtrationfiltered through celite and
  3. concentrationconcentrated
  4. customPurification via flash column chromatography (0.5:9.5, MeOH:CH2Cl2)

Sources & evidence

ORD record
ord-e922d2202096440b955c6df01fc5749f
Source dataset
uspto-grants-2013_01
Patent number
US08357697B2

Reaction notes

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