Triacetoxyperiodinane → HCID 86618445, compound

HRID 2262243Notes

Reaction equation

HRID 2262243 reaction equation
[OH:1][CH2:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[Cl:38][C:39]1[N:40]=[C:41]([N:48]2[CH2:53][CH2:52][O:51][CH2:50][CH2:49]2)[C:42]2[S:47][CH:46]=[CH:45][C:43]=2[N:44]=1.C(C1CCN(C(OC(C)(C)C)=O)CC1)=O>ClCCl>[Cl:38][C:39]1[N:40]=[C:41]([N:48]2[CH2:53][CH2:52][O:51][CH2:50][CH2:49]2)[C:42]2[S:47][C:46]([CH:2]([OH:1])[CH:3]3[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]3)=[CH:45][C:43]=2[N:44]=1

Participants

6

Reactant 4

HCID 159087TriacetoxyperiodinaneHCID 1514430tert-Butyl 4-formylpiperidine-1-carboxylateHCID 2764081Tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylateHCID 202849712-Chloro-4-(morpholin-4-yl)thieno(3,2-d)pyrimidine

Product 1

HCID 86618445HCID 86618445, compoundYield 21%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate (1 g) in 20 mL of dichloromethane was combined with 2 g of Dess-Martin periodinane and stirred for 2 h, filtered through celite, extracted with saturated sodium bicarbonate, and evaporated. The crude product was placed on a column and 325 mg of the aldehyde, tert-butyl 4-formylpiperidine-1-carboxylate, was isolated. 260 mg 2-chloro-4-morpholinothieno[3,2-d]pyrimidine 4 was reacted with 325 mg of tert-butyl 4-formylpiperidine-1-carboxylate following General Procedure D to give 100 mg of tert-butyl 4-((2-chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)(hydroxy)methyl)piperidine-1-carboxylate. The Boc group was removed from 100 mg of the alcohol using 0.125 mL of a 4.0 M HCl solution in dioxane in 10 mL of DCM with 0.5 mL of methanol. After several hours the DCM, methanol, and HCl was evaporated. The crude amine, (2-chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)(piperidin-4-yl)methanol, was mesylated in 3 mL of DCM and 0.04 mL of triethylamine with 0.03 mL of methanesulfonyl chloride. The 4-N-methylsulfonylpiperidinyl compound was then coupled to 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)1H-indazole 7 following General Procedure A to give 70 mg of 353 after reversed phase HPLC purification. MS (Q1) 530 (M)+

Workup

  1. filtrationfiltered through celite
  2. extractionextracted with saturated sodium bicarbonate
  3. customevaporated
  4. customwas isolated

Sources & evidence

ORD record
ord-ef863dab8d5846c3885cc9c353d1aae2
Source dataset
uspto-grants-2010_12
Patent number
US07846929B2

Reaction notes

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