Sodium Carbonate → {1-(4-Chlorobenzyl)-2-oxo-2-[4-(6-thiophen-3-yl-thieno[3,2-d]pyrimidin-4-yl)-piperazin-1-yl]-ethyl}-carbamic acid tert-butyl ester

HRID 1192311Notes

Reaction equation

HRID 1192311 reaction equation
[C:1]([O:5][C:6](=[O:35])[NH:7][CH:8]([CH2:27][C:28]1[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=1)[C:9]([N:11]1[CH2:16][CH2:15][N:14]([C:17]2[C:18]3[S:25][C:24](I)=[CH:23][C:19]=3[N:20]=[CH:21][N:22]=2)[CH2:13][CH2:12]1)=[O:10])([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[Na+].[Na+].[S:42]1[CH:46]=[CH:45][C:44](B(O)O)=[CH:43]1>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([O:5][C:6](=[O:35])[NH:7][CH:8]([CH2:27][C:28]1[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=1)[C:9](=[O:10])[N:11]1[CH2:16][CH2:15][N:14]([C:17]2[C:18]3[S:25][C:24]([C:44]4[CH:45]=[CH:46][S:42][CH:43]=4)=[CH:23][C:19]=3[N:20]=[CH:21][N:22]=2)[CH2:13][CH2:12]1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 581760Thiophene-3-boronic acidHCID 67538988{1-(4-Chlorobenzyl)-2-[4-(6-iodothieno[3,2-d]pyrimidin-4-yl)-piperazin-1-yl]-2-oxo-ethyl}-carbamic acid tert-butyl ester

Product 1

HCID 67539661{1-(4-Chlorobenzyl)-2-oxo-2-[4-(6-thiophen-3-yl-thieno[3,2-d]pyrimidin-4-yl)-piperazin-1-yl]-ethyl}-carbamic acid tert-butyl esterYield 34.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of {1-(4-chlorobenzyl)-2-[4-(6-iodothieno[3,2-d]pyrimidin-4-yl)-piperazin-1-yl]-2-oxo-ethyl}-carbamic acid tert-butyl ester (50 mg, 0.080 mmol) in DMF (3 mL) were added 2M Na2CO3 (0.1 mL) and 3-thiophenyl boronic acid (15 mg, 0.117 mmol). The mixture was bubbled N2 for 20 minutes and then Pd(PPh3)4 (10 mg, 0.012 mmol) was added. The mixture was heated to 90° C. for 12 hours. The solvent was removed under vacuum and the residue was subject to chromatography on silica gel to afford the product {1-(4-chlorobenzyl)-2-oxo-2-[4-(6-thiophen-3-yl-thieno[3,2-d]pyrimidin-4-yl)-piperazin-1-yl]-ethyl}-carbamic acid tert-butyl ester (16 mg, 34.4%). 1H NMR (CDCl3, 400 Hz) δ 8.57 (s, 1H), 7.70-7.42 (m, 4H), 7.27 (d, J=8.4, 2H), 7.16 (d, J=8.4 Hz, 2H), 5.36 (d, J=8.8 Hz, 1H), 4.87-4.84 (m, 1H), 3.91-3.59 (m, 7H), 3.27-3.24 (d, J=11.2 Hz, 1H), 3.00-2.99 (d, J=7.2 Hz, 2H), 1.43 (s, 9H). MS (ESI+) [M+H]+ 584.

Workup

  1. customThe mixture was bubbled N2 for 20 minutes
  2. customThe solvent was removed under vacuum

Sources & evidence

ORD record
ord-14bdb647d6ba479db133ef657a2e8749
Source dataset
uspto-grants-2014_03
Patent number
US08680114B2

Reaction notes

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