3,4-Dichlorobenzaldehyde → HCID 22115321, compound

HRID 1276370Notes

Reaction equation

HRID 1276370 reaction equation
[NH:1]1[CH2:5][CH2:4][CH:3]([CH2:6][NH:7][C:8](=[O:25])[CH2:9][O:10][C:11]2[N:16]=[CH:15][C:14]([C:17]3[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=3)=[CH:13][N:12]=2)[CH2:2]1.[Cl:26][C:27]1[CH:28]=[C:29]([CH:32]=[CH:33][C:34]=1[Cl:35])[CH:30]=O.C(N(C(C)C)CC)(C)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClC(Cl)C>[Cl:26][C:27]1[CH:28]=[C:29]([CH:32]=[CH:33][C:34]=1[Cl:35])[CH2:30][N:1]1[CH2:5][CH2:4][CH:3]([CH2:6][NH:7][C:8](=[O:25])[CH2:9][O:10][C:11]2[N:12]=[CH:13][C:14]([C:17]3[CH:18]=[CH:19][C:20]([O:23][CH3:24])=[CH:21][CH:22]=3)=[CH:15][N:16]=2)[CH2:2]1

Participants

6

Reactant 4

HCID 227103,4-DichlorobenzaldehydeHCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 22115344HCID 22115344, compound

Product 1

HCID 22115321HCID 22115321, compound

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent2×

Procedure

A stock solution containing N-(pyrrolidin-3-(RS)-ylmethyl)-2-(5-(4-methoxyphenyl)pyrimidin-2-yloxy)acetamide (0.44 mmol) in dichloroethane (10 mL) was added to a solution of 3,4-dichlorobenzaldehyde (85 mg, 0.48 mmol, 1.1 equiv.) and diisopropylethylamine (0.35 mL, 2.0 mmol, 4.5 equiv.) in dichloroethane (5 mL). Excess Na(OAc)3BH (140 mg, 0.66 mmol, 1.5 equiv.) was added and the reaction mixture was stirred rapidly at room temperature overnight. The reaction mixture was quenched with methanol, concentrated and diluted with 1:1 methanol/dimethyl sulfoxide. The solution was then purified directly using preparative reverse phase chromatography to give, after treatment with 4 M hydrochloric acid in dioxane (1 mL) and concentration, N-[1-(3,4-dichlorobenzyl)pyrrolidin-3-(RS)-ylmethyl]-2-[5-(4-methoxyphenyl)pyrimidin-2-yloxy]-acetamide HCl salt (96 mg).

Workup

  1. customThe reaction mixture was quenched with methanol
  2. concentrationconcentrated
  3. additiondiluted with 1:1 methanol/dimethyl sulfoxide
  4. customThe solution was then purified directly
  5. customto give
  6. concentrationafter treatment with 4 M hydrochloric acid in dioxane (1 mL) and concentration, N-[1-(3,4-dichlorobenzyl)pyrrolidin-3-(RS)-ylmethyl]-2-[5-(4-methoxyphenyl)pyrimidin-2-yloxy]-acetamide HCl salt (96 mg)

Sources & evidence

ORD record
ord-d86ca6c477b04d9c9f3588d8fa087440
Source dataset
uspto-grants-2000_12
Patent number
US06166015

Reaction notes

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