Carbon tetrabromide → HCID 58671559, compound

HRID 1811564Notes

Reaction equation

HRID 1811564 reaction equation
[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:19]([O:20][CH3:21])=[C:18]([NH:22][C:23]3[C:24]([CH3:32])=[N:25][C:26]([CH2:29][CH2:30]O)=[CH:27][CH:28]=3)[N:17]=[CH:16][N:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.BrC(Br)(Br)Br.[OH-].[Na+].S(O)(O)(=O)=O.[CH3:64][S:65]C(=N)N>C(Cl)Cl.CO>[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:19]([O:20][CH3:21])=[C:18]([NH:22][C:23]3[C:24]([CH3:32])=[N:25][C:26]([CH2:29][CH2:30][S:65][CH3:64])=[CH:27][CH:28]=3)[N:17]=[CH:16][N:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2]

Participants

8

Reactant 5

HCID 11205Carbon tetrabromideHCID 11776TriphenylphosphineHCID 14798Sodium HydroxideHCID 752702-Methyl-2-thiopseudourea sulfateHCID 11683750HCID 11683750, compound

Product 1

HCID 58671559HCID 58671559, compoundYield 23.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To an ice-cooled solution of 4-{6-[6-(2-hydroxy-ethyl)-2-methyl-pyridin-3-ylamino]-5-methoxy-pyrimidin-4-yloxy}-piperidine-1-carboxylic acid isopropyl ester (40.2 mg, 90.2 μmol) and triphenylphosphine (31 mg, 118 pmol) in 2 mL methylene chloride, perbromomethane (77.0 mg, 232 μmol) were added and solution was stirred at room temperature. After 18 h, the mixture was concentrated, re-dissolved in 1.5 mL MeOH, and added to a well stirred mixture of sodium hydroxide (120 mg, 3.0 mmol) and 2-methyl-2-thiopseudourea sulfate (208 mg, 0.70 mmol) in 2 mL MeOH. After stirring at room temperature for 17 h, mixture was concentrated and extracted with water and methylene chloride. Organic phases were concentrated and purified by HPLC to give 4-{5-methoxy-6-[2-methyl-6-(2-methylsulfanyl-ethyl)-pyrdin-3-ylamino]-pyrimidin-4-yloxy}-piperidine-1-carboxylic acid isopropyl ester (TFA salt, 10.0 mg, 19%) as a white solid. 1HNMR (MeOH-d4, 400 MHz) δ 1.21-1.23 (d, J=6.2 Hz, 6H), 1.72-1.78 (m, 2H), 1.94-2.01 (m, 2H), 2.12 (s, 3H), 2.65 (s, 3H), 2.90-2.93 (t, J=7.2 Hz, 2H), 3.24-3.27 (t, J=7.2 Hz, 2H), 3.39-3.46 (m, 2H), 3.69-3.76 (m, 2H), 3.91 (s, 3H), 4.80-4.86 (m, 2H), 5.32-5.38 (m, 1H), 7.75-7.77 (d, J=8.6 Hz, 1H), 7.96 (s, 1H), 8.57-5.59 (d, J=8.6 Hz, 1H). Exact mass calculated for C23H33N5O4S 475.23 found 476.2 (MH+).

Workup

  1. additionwere added
  2. concentrationthe mixture was concentrated
  3. dissolutionre-dissolved in 1.5 mL MeOH
  4. additionadded to a well
  5. stirringstirred
  6. stirringAfter stirring at room temperature for 17 h
  7. concentrationmixture was concentrated
  8. extractionextracted with water and methylene chloride
  9. concentrationOrganic phases were concentrated
  10. custompurified by HPLC

Sources & evidence

ORD record
ord-e3cb3c7ec3cd42a1b0d7047a79fff591
Source dataset
uspto-grants-2013_01
Patent number
US08362248B2

Reaction notes

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