Formaldehyde → HCID 68906214, compound

HRID 1986292Notes

Reaction equation

HRID 1986292 reaction equation
[ClH:1].Cl.[CH:3]1([NH:6][C:7]([C:9]2[C:17]3[CH:16]=[C:15]([C:18]4[C:23]([Br:24])=[CH:22][N:21]=[C:20]([NH:25][CH2:26][CH2:27][C:28]5([CH3:34])[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]5)[N:19]=4)[S:14][C:13]=3[CH:12]=[CH:11][CH:10]=2)=[O:8])[CH2:5][CH2:4]1.[Cl:35][CH2:36]Cl.C=O.[BH4-].[Na+]>CO>[ClH:35].[ClH:1].[CH:3]1([NH:6][C:7]([C:9]2[C:17]3[CH:16]=[C:15]([C:18]4[C:23]([Br:24])=[CH:22][N:21]=[C:20]([NH:25][CH2:26][CH2:27][C:28]5([CH3:34])[CH2:33][CH2:32][N:31]([CH3:36])[CH2:30][CH2:29]5)[N:19]=4)[S:14][C:13]=3[CH:12]=[CH:11][CH:10]=2)=[O:8])[CH2:4][CH2:5]1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 6344DichloromethaneHCID 4311764Sodium borohydride2×HCID 68856361HCID 68856361, compound

Product 1

HCID 68906214HCID 68906214, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To 2-{5-bromo-2-[2-(4-methylpiperidin-4-yl)-ethylamino]-pyrimidin-4-yl}-benzo[b]thiophene-4-carboxylic acid cyclopropylamide dihydrochloric acid (0.200 g, 0.34 mmol) dissolved in 3:1 MeOH:dichloromethane (8 mL) is added 37.4% aqueous formaldehyde (0.076 mL, 1.02 mmol). After 1 hour, the reaction mixture is cooled in an ice bath and sodium borohydride is added in portions over two minutes. The reaction proceeds for 1 hour in an ice bath and 1 hour at room temperature. By TLC an intermediate is present and an additional equivalent of sodium borohydride is added at 0° C. After 30 minutes the entire reaction mixture is loaded onto a silica gel column and chromatographed, eluting with 3-7% (2 M NH3 in MeOH) in dichloromethane to give 116 mg, 64% yield, of the methylated product. It is converted to the titled compound by treating with concentrated HCl solution and isolated as a yellow solid. ES+(m/z) 528 (79Br) and 530 (81Br) [M(free base)+H].

Workup

  1. temperaturethe reaction mixture is cooled in an ice bath
  2. waitThe reaction proceeds for 1 hour in an ice bath and 1 hour at room temperature
  3. customAfter 30 minutes the entire reaction mixture
  4. customchromatographed
  5. washeluting with 3-7% (2 M NH3 in MeOH) in dichloromethane
  6. customto give 116 mg, 64% yield

Sources & evidence

ORD record
ord-879a91fe4958483d9450b8cd2633af71
Source dataset
uspto-grants-2009_06
Patent number
US07547691B2

Reaction notes

Loading…