Acetic Acid → (2-Chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidine-6-ylmethyl)-(1-methanesulphonyl-piperidin-4-yl)-methyl-amine

HRID 888942Notes

Reaction equation

HRID 888942 reaction equation
[CH3:1][S:2]([N:5]1[CH2:10][CH2:9][C:8](=O)[CH2:7][CH2:6]1)(=[O:4])=[O:3].[Cl:12][C:13]1[N:18]=[C:17]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)[C:16]2[S:25][C:26]([CH2:28][NH:29][CH3:30])=[CH:27][C:15]=2[N:14]=1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.ClCCl>[Cl:12][C:13]1[N:18]=[C:17]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)[C:16]2[S:25][C:26]([CH2:28][N:29]([CH:8]3[CH2:9][CH2:10][N:5]([S:2]([CH3:1])(=[O:4])=[O:3])[CH2:6][CH2:7]3)[CH3:30])=[CH:27][C:15]=2[N:14]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 120720291-(Methylsulphonyl)piperidin-4-oneHCID 595929371-(2-Chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)-N-methylmethanamine

Product 1

HCID 86638094(2-Chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidine-6-ylmethyl)-(1-methanesulphonyl-piperidin-4-yl)-methyl-amineYield 91.1%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-methanesulfonyl-piperidine-4-one (173 mg; prepared from N-BOC-piperidone by reaction of piperidone-4-one TFA salt with methane sulfonyl chloride) stirring in anhydrous 1,2-dichloroethane (10 ml), was added 2-chloro-4-morpholin-4-yl-thienopyrimidine-6-ylmethyl methylamine (291 mg; as prepared from 2-chloro-4-morpholin-4-yl-thienopyrimidine-6-carbaldehyde and methylamine under reductive amination conditions), followed by glacial acetic acid (59 μl). Sodium triacetoxyborohydride (269 mg) was added in several aliquots and then stirred for 12 hours at room temperature. The reaction mixture was diluted with dichloromethane (30 ml) and washed with 50% sodium hydrogen carbonate solution, brine, and dried (MgSO4). The solvents were removed in vacuo to give a residue which after purification by flash silica chromatography gave (2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidine-6-ylmethyl)-(1-methanesulphonyl-piperidin-4-yl)-methyl-amine (408 mg), which was used in a Suzuki coupling with 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-indole, to give, after flash silica purification the title compound (55 mg) as a white solid.

Workup

  1. washwashed with 50% sodium hydrogen carbonate solution, brine
  2. dry with materialdried (MgSO4)
  3. customThe solvents were removed in vacuo
  4. customto give a residue which
  5. customafter purification by flash silica chromatography

Sources & evidence

ORD record
ord-4acef2463a4540c8b763c66188944d8d
Source dataset
uspto-grants-2012_08
Patent number
US08252792B2

Reaction notes

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