Dimethylcarbamoyl Chloride → (R)-tetrahydrofuran-3-yl 3-(2-(dimethylcarbamoyl)-2,3-dihydro-1H-spiro[isoquinoline-4,4'-piperidine]-1'-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate

HRID 251479Notes

Reaction equation

HRID 251479 reaction equation
[N:1]1([CH:16]2[CH2:22][CH:21]3[N:23]([C:24]([O:26][C@@H:27]4[CH2:31][CH2:30][O:29][CH2:28]4)=[O:25])[CH:18]([CH2:19][CH2:20]3)[CH2:17]2)[CH2:6][CH2:5][C:4]2([C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH2:9][NH:8][CH2:7]2)[CH2:3][CH2:2]1.[CH3:32][N:33]([CH3:37])[C:34](Cl)=[O:35].C(N(C(C)C)CC)(C)C>C(Cl)Cl>[CH3:32][N:33]([CH3:37])[C:34]([N:8]1[CH2:7][C:4]2([CH2:3][CH2:2][N:1]([CH:16]3[CH2:22][CH:21]4[N:23]([C:24]([O:26][C@@H:27]5[CH2:31][CH2:30][O:29][CH2:28]5)=[O:25])[CH:18]([CH2:19][CH2:20]4)[CH2:17]3)[CH2:6][CH2:5]2)[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:9]1)=[O:35]

Participants

5

Reactant 3

HCID 6598Dimethylcarbamoyl ChlorideHCID 81531DiisopropylethylamineHCID 67147257(R)-tetrahydrofuran-3-yl 3-(2,3-dihydro-1H-spiro[isoquinoline-4,4-piperidine]-1'-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate

Product 1

HCID 11992810(R)-tetrahydrofuran-3-yl 3-(2-(dimethylcarbamoyl)-2,3-dihydro-1H-spiro[isoquinoline-4,4'-piperidine]-1'-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

(R)-tetrahydrofuran-3-yl 3-(2,3-dihydro-1H-spiro[isoquinoline-4,4-piperidine]-1′-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate (20 mg, 0.047 mmol) was dissolved in CH2Cl2 (1 mL) and treated with a solution of dimethylcarbamic chloride (20 mg, 0.13 mmol) in CH2Cl2 (100 μL). A solution of diisopropyl ethylamine (20 μL, 14.8 mg, 0.11 mmol) was added. The resulting mixture was allowed to stand at room temperature for 10 min and was then purified by LC/MS (10-99% CH3CN—H2O, with 0.03% TFA, 9 min) to provide (R)-tetrahydrofuran-3-yl 3-(2-(dimethylcarbamoyl)-2,3-dihydro-1H-spiro[isoquinoline-4,4′-piperidine]-1′-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate. LC/MS m/z [M+H]+ 497.4, retention time 2.15 min (10-99% CH3CN—H2O gradient, with 0.05% TFA, 5 min).

Workup

  1. customwas then purified by LC/MS (10-99% CH3CN—H2O, with 0.03% TFA, 9 min)

Sources & evidence

ORD record
ord-f858c9f018044c5eb15fc5bad0874a65
Source dataset
uspto-grants-2011_01
Patent number
US07863449B2

Reaction notes

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