5-(Tributylstannyl)-1,3-thiazole → 4-morpholino-6-((4-N-methylsulfonylpiperazin-1-yl)methyl)-2-(thiazol-5-yl)thieno[3,2-d]pyrimidine

HRID 390864

Reaction equation

HRID 390864 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[C:5]2[S:10][C:9]([CH2:11][N:12]3[CH2:17][CH2:16][N:15]([S:18]([CH3:21])(=[O:20])=[O:19])[CH2:14][CH2:13]3)=[CH:8][C:6]=2[N:7]=1.C([Sn](CCCC)(CCCC)[C:33]1[S:37][CH:36]=[N:35][CH:34]=1)CCC>CC(N(C)C)=O.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>[O:25]1[CH2:26][CH2:27][N:22]([C:4]2[C:5]3[S:10][C:9]([CH2:11][N:12]4[CH2:17][CH2:16][N:15]([S:18]([CH3:21])(=[O:20])=[O:19])[CH2:14][CH2:13]4)=[CH:8][C:6]=3[N:7]=[C:2]([C:33]3[S:37][CH:36]=[N:35][CH:34]=3)[N:3]=2)[CH2:23][CH2:24]1

Participants

5

Reactant 2

HCID 27632575-(Tributylstannyl)-1,3-thiazoleHCID 236508374-(2-Chloro-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)thieno[3,2-d]pyrimidin-4-yl)morpholine

Product 1

HCID 582340444-morpholino-6-((4-N-methylsulfonylpiperazin-1-yl)methyl)-2-(thiazol-5-yl)thieno[3,2-d]pyrimidineYield 50%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
150 °C

Procedure

A suspension of 2-chloro-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine, prepared via General Procedure B-3, (144 mg, 0.33 mmol), 5-tributylstannanyl-thiazole (187 mg, 0.5 mmol), and Pd(PPh3)4 (19 mg, 0.017 mmol) in anhydrous DMA was heated in a microwave at 150° C. for 10 mins. The crude reaction was loaded onto a preconditioned SCX cartridge, washing the cartridge with methanol and dichloromethane before eluting with 7N ammonia in methanol to give crude material. This was purified by on silica using 5% methanol in ethyl acetate as the eluent to give 152 as an off-white solid (80 mg, 50%). NMR (CDCl3, 400 MHz), 2.68-2.72 (4H, m), 2.83 (3H, s), 3.32-3.36 (4H, m), 3.88-3.93 (6H, m), 4.03-4.06 (4H, m), 7.32 (1H, s), 8.67 (1H, m), 8.84 (1H, s). MS: (ESI+): MH+=481

Workup

  1. customThe crude reaction
  2. washwashing the cartridge with methanol and dichloromethane
  3. washbefore eluting with 7N ammonia in methanol
  4. customto give crude material
  5. customThis was purified by on silica using 5% methanol in ethyl acetate as the eluent

Sources & evidence

ORD record
ord-0e0f3e8f7b7146c692ea2f769a0a9710
Source dataset
uspto-grants-2013_02
Patent number
US08383620B2

Linked notes

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