Tetrahydrofuran → HCID 66977618, compound

HRID 1255817Notes

Reaction equation

HRID 1255817 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][C:9]([N:12]([CH2:14][C:15]2[S:23][C:22]3[C:21]([N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[N:20][C:19]([C:30]4[CH:35]=[CH:34][CH:33]=[C:32]([O:36][CH2:37][CH2:38][O:39][Si](C(C)(C)C)(C)C)[CH:31]=4)=[N:18][C:17]=3[CH:16]=2)[CH3:13])=[N:10][CH:11]=1)=[O:5])[CH3:2].C1COCC1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C(OCC)(=O)C>[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][C:9]([N:12]([CH2:14][C:15]2[S:23][C:22]3[C:21]([N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[N:20][C:19]([C:30]4[CH:35]=[CH:34][CH:33]=[C:32]([O:36][CH2:37][CH2:38][OH:39])[CH:31]=4)=[N:18][C:17]=3[CH:16]=2)[CH3:13])=[N:10][CH:11]=1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 2724141Tetrabutylammonium FluorideHCID 66977714HCID 66977714, compound

Product 1

HCID 66977618HCID 66977618, compoundYield 96.1%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 0602-289 (1.94 g, 5.1 mmol), 0504 (0.5079 g, 1.3 mmol) and NaHCO3 (0.323 g, 3.8 mmol) were taken into 10 ml toluene (10 mL), ethanol (6.4 mL) and water (2.8 mL) followed the addition of Pd(PPh3)2Cl2 (54 mg). The resulting mixture was heated at 120° C. overnight. TLC showed the reaction complete. The reaction mixture was filtered through celite and washed with dichloromethane. The crude product was purified by column chromatography eluted with hexanes/ethyl acetate to afford 2-[(2-{3-[2-(tert-Butyl-dimethyl-silanyloxy)-ethoxy]-phenyl}-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-methyl-amino]-pyrimidine-5-carboxylic acid ethyl ester (0.71 g, 83%) as an off-white solid. LC-MS: 665 [M+1]+. 2-[(2-{3-[2-(tert-Butyl-dimethyl-silanyloxy)-ethoxy]-phenyl}-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-methyl-amino]-pyrimidine-5-carboxylic acid ethyl ester (680 mg, 1.02 mmol) was taken into THF (20 mL) followed by the addition of tetrabutyl ammonium fluoride (533 mg, 2.04 mmol). The resulting mixture was stirred at room temperature for 30 min. TLC showed reaction complete. Reaction mixture was diluted with ethyl acetate, washed with water and dried with Na2SO4. The crude product was purified by column chromatography eluted with hexanes/ethyl acetate to afford titled compound as an off-white solid (540 mg, 96%). m.p.: 216-220° C. LC-MS: 551.3 [M+1]+. 1H NMR (400 MHz, CDCl3): δ 1.38 (t, J=6.8 Hz, 3H), 3.31 (s, 3H), 3.86 (t, J=5.2 Hz, 4H), 3.99-4.02 (m, 6H), 4.20 (t, J=4.4 Hz, 2H), 4.37 (q, J=7.2 Hz, 2H), 5.19 (s, 2H). 7.01 (dd, J=8 Hz, 2 Hz, 1H), 7.35-7.39 (m, 2H). 8.01-8.05 (m, 2H), 8.92 (s, 2H).

Workup

  1. customreaction complete
  2. customReaction mixture
  3. washwashed with water
  4. dry with materialdried with Na2SO4
  5. customThe crude product was purified by column chromatography
  6. washeluted with hexanes/ethyl acetate

Sources & evidence

ORD record
ord-bf488ddfe7b04d7fa312bb0ffe67f897
Source dataset
uspto-grants-2013_06
Patent number
US08461157B2

Reaction notes

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