Dichloromethane → HCID 67105546, compound

HRID 729965Notes

Reaction equation

HRID 729965 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:23]=[CH:22][C:12]([O:13][C:14]3[CH:19]=[CH:18][N:17]=[C:16]([C:20]#[N:21])[CH:15]=3)=[CH:11][CH:10]=2)[CH:5]=[C:4]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[N:3]=1.C([O-])(=O)C.[Na+].[Br:35]Br.ClCCl>C(O)(=O)C.O>[NH2:1][C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:23]=[CH:22][C:12]([O:13][C:14]3[CH:19]=[CH:18][N:17]=[C:16]([C:20]#[N:21])[CH:15]=3)=[CH:11][CH:10]=2)[C:5]([Br:35])=[C:4]([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[N:3]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 24408BromineHCID 517045Sodium AcetateHCID 57833365HCID 57833365, compound

Product 1

HCID 67105546HCID 67105546, compoundYield 83%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Procedure

To a solution of 4-[4-(2-amino-6-phenyl-pyrimidin-4-ylamino)-phenoxy]-pyridine-2-carbonitrile (Example 8, 200 mg, 0.53 mmol) and sodium acetate (146.6 mg, 459.8 mmol) in acetic acid (4 mL) at rt was added bromine (84 mg, 0.53 mmol). The reaction was allowed to stand for 2 h after which time dichloromethane (20 mL) was added followed by water (20 mL). The phases were separated and the organic layer was washed with a saturated aqueous bicarbonate solution. The combined organic extracts were dried over MgSO4 and then evaporated under vacuum. The crude material was purified by column chromatography eluting with a gradient of 0 to 60% AcOEt/Hexanes to give 4-[4-(2-Amino-5-bromo-6-phenyl-pyrimidin-4-ylamino)-phenoxy]-pyridine-2-carbonitrile as an orange solid (200 mg, 83%). 1H NMR (DMSO d6) δ 8.58 (d, J=5 Hz, 1H, 8.50 (Br, 1H), 7.90-7.86 (m, 2H), 7.67 (d, J=2 Hz, 1H), 7.54-7.51 (m, 2H), 7.47-7.41 (m, 3H), 7.20-7.16 (m, 3H), 6.57 (Br, 2H). MS ES 459 (M+H)+, calcd 459, RT=2.85 min.

Workup

  1. customThe phases were separated
  2. washthe organic layer was washed with a saturated aqueous bicarbonate solution
  3. dry with materialThe combined organic extracts were dried over MgSO4
  4. customevaporated under vacuum
  5. customThe crude material was purified by column chromatography
  6. washeluting with a gradient of 0 to 60% AcOEt/Hexanes

Sources & evidence

ORD record
ord-d7e92e0cc920419eb77a716daa86de1b
Source dataset
uspto-grants-2009_09
Patent number
US07582646B2

Reaction notes

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