Acetic Acid → N-[[1-(2-chloro-5-phenyl-thieno[2,3-d]pyrimidin-4-yl)-4-piperidyl]methyl]-N,1-dimethyl-pyrrolidin-3-amine

HRID 928560Notes

Reaction equation

HRID 928560 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[Cl:15][C:16]1[N:17]=[C:18]([N:31]2[CH2:36][CH2:35][CH:34]([CH:37]=O)[CH2:33][CH2:32]2)[C:19]2[C:24]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[CH:23][S:22][C:20]=2[N:21]=1.[CH3:39][NH:40][CH:41]1[CH2:45][N:44]([CH3:46])[CH2:43][CH2:42]1.C(O)(=O)C>ClCCl.O>[Cl:15][C:16]1[N:17]=[C:18]([N:31]2[CH2:36][CH2:35][CH:34]([CH2:37][N:40]([CH3:39])[CH:41]3[CH2:42][CH2:43][N:44]([CH3:46])[CH2:45]3)[CH2:33][CH2:32]2)[C:19]2[C:24]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[CH:23][S:22][C:20]=2[N:21]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 2758520N,1-dimethylpyrrolidin-3-amineHCID 5049666Sodium triacetoxyborohydrideHCID 895795321-(2-Chloro-5-phenyl-thieno[2,3-d]pyrimidin-4-yl)piperidine-4-carbaldehyde

Product 1

HCID 89583670N-[[1-(2-chloro-5-phenyl-thieno[2,3-d]pyrimidin-4-yl)-4-piperidyl]methyl]-N,1-dimethyl-pyrrolidin-3-amine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Sodium triacetoxyborohydride (1.54 g, 7.28 mmol) was added to a stirred solution of 1-(2-chloro-5-phenyl-thieno[2,3-d]pyrimidin-4-yl)piperidine-4-carbaldehyde (1.3 g, 3.64 mmol), N,N′-dimethyl-3-aminopyrrolidine (519 ul, 4.00 mmol) and acetic acid (240 ul, 4.00 mmol) in dry dichloromethane (20 ml) at room temperature. The solution was stirred for ˜2 h, after which time the reaction had reached completion. Water (20 ml) was added and the organic layer separated, the aqueous phase was extracted with dichloromethane (×3) and the combined organics washed with brine, then dried (MgSO4) and evaporated. The crude residue was purified by flash column chromatography (0 to 5% 7.0M NH3/MeOH in dichloromethane). N—[[1-(2-chloro-5-phenyl-thieno[2,3-d]pyrimidin-4-yl)-4-piperidyl]methyl]-N,1-dimethyl-pyrrolidin-3-amine was isolated as a pale yellow oil (1.25 g, 76%). LCMS: (M+H)+ 456.2, RT=2.99.

Workup

  1. customthe organic layer separated
  2. extractionthe aqueous phase was extracted with dichloromethane (×3)
  3. washthe combined organics washed with brine
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customThe crude residue was purified by flash column chromatography (0 to 5% 7.0M NH3/MeOH in dichloromethane)

Sources & evidence

ORD record
ord-47f88e3f799d43e09444c5c091ea7533
Source dataset
uspto-grants-2016_03
Patent number
US09290511B2

Reaction notes

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