Ethyl orthoformate → HCID 53630423, compound

HRID 1864164Notes

Reaction equation

HRID 1864164 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[C:20]([NH2:21])=[C:19]([NH:22][C:23]3[CH:28]=[CH:27][C:26]([S:29]([CH3:32])(=[O:31])=[O:30])=[CH:25][CH:24]=3)[N:18]=[CH:17][N:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:33](OCC)(OCC)OCC>C(OC(=O)C)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[N:16]=[CH:17][N:18]=[C:19]3[C:20]=2[N:21]=[CH:33][N:22]3[C:23]2[CH:24]=[CH:25][C:26]([S:29]([CH3:32])(=[O:31])=[O:30])=[CH:27][CH:28]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 31214Ethyl orthoformateHCID 53630454HCID 53630454, compound

Product 1

HCID 53630423HCID 53630423, compound

Reagents, catalysts & solvents 1

HCID 7918Acetic AnhydrideSolvent

Conditions

Temperature
140 °C

Procedure

4-[5-Amino-6-(4-methanesulfonyl-phenylamino)-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid tert-butyl ester (300 mg, 0.6 mmol) was dissolved in mixture of triethyl orthoformate (4 mL) and acetic anhydride (4 mL), and then the mixture was refluxed at 140° C. for 15 hours. The crude product was quenched with saturated sodium bicarbonate and extracted with ethyl acetate, then dried in vacuo. Solid was precipitated out in acetonitrile/water and provided Compound B4 as a peach solid (205 mg, 67%). 1H NMR (CDCl3, 400MHz) δ 1.48 (s, 9H), 1.95-1.91 (m, 2H), 2.14-2.11 (m, 2H), 3.12 (s, 3H), 3.34-3.27 (m, 2H), 3.94-3.91 (m, 2H), 5.61 (m, 1H), 8.06 (d, 2H), 8.19 (d, 2H), 8.29 (s, 1H), 8.61 (s, 1H). Exact mass calculated for C22H27N5O5S 473.17, found 474.3 (MH+).

Workup

  1. customThe crude product was quenched with saturated sodium bicarbonate
  2. extractionextracted with ethyl acetate
  3. customdried in vacuo
  4. customSolid was precipitated out in acetonitrile/water

Sources & evidence

ORD record
ord-ff8f77b3ac8740d895de091889a36e13
Source dataset
uspto-grants-2009_12
Patent number
US07625906B2

Reaction notes

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