Hydrogen Bromide → HCID 86268247, compound

HRID 710011Notes

Reaction equation

HRID 710011 reaction equation
C[O:2][C:3]1[C:8]([C:9]2[CH:14]=[CH:13][C:12]([O:15][C:16]3[CH:21]=[CH:20][N:19]=[C:18]([C:22]4[CH:23]=[N:24][N:25]([CH3:27])[CH:26]=4)[CH:17]=3)=[C:11]([CH3:28])[N:10]=2)=[CH:7][N:6]=[C:5]([NH:29][CH2:30][C:31]([CH3:34])([CH3:33])[CH3:32])[N:4]=1.Br.CCOC(C)=O>C(O)(=O)C>[CH3:28][C:11]1[N:10]=[C:9]([C:8]2[C:3](=[O:2])[NH:4][C:5]([NH:29][CH2:30][C:31]([CH3:34])([CH3:32])[CH3:33])=[N:6][CH:7]=2)[CH:14]=[CH:13][C:12]=1[O:15][C:16]1[CH:21]=[CH:20][N:19]=[C:18]([C:22]2[CH:23]=[N:24][N:25]([CH3:27])[CH:26]=2)[CH:17]=1

Participants

5

Reactant 3

HCID 260Hydrogen BromideHCID 8857Ethyl AcetateHCID 90416458HCID 90416458, compound

Product 1

HCID 86268247HCID 86268247, compoundYield 56.1%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 4-methoxy-5-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-N-neopentylpyrimidin-2-amine (0.081 g, 0.176 mmol) in acetic acid (2 mL) was treated with HBr (48% aq, 0.080 mL, 0.705 mmol), heated at 80° C. for 6 h, then cooled to RT overnight. The mixture was treated with ice and EtOAc, neutralized with satd. NaHCO3, extracted with EtOAc (3×) and the combined organics were washed with brine, dried over MgSO4 and concentrated to dryness. The material was suspended in MeCN, heated to near-reflux and allowed to stand at RT for 3 h. The resulting solid was collected via filtration to afford 5-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-(neopentylamino)pyrimidin-4(3H)-one (44 mg, 56%). 1H NMR (400 MHz, DMSO-d6): δ 10.84 (s, 1H), 8.68 (s, 1H), 8.35 (d, J=6.6 Hz, 1H), 8.28-8.23 (m, 2H), 7.96 (s, 1H), 7.52 (d, J=8.6 Hz, 1H), 7.22 (d, J=3.0 Hz, 1H), 6.73 (br s, 1H), 6.60 (dd, J=5.1, 2.3 Hz, 1H), 3.86 (s, 3H), 3.22 (d, J=6.2 Hz, 2H), 2.34 (s, 3H), 0.91 (s, 9H); MS (ESI) m/z: 446.2 (M+H+).

Workup

  1. temperaturecooled to RT overnight
  2. extractionNaHCO3, extracted with EtOAc (3×)
  3. washthe combined organics were washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated to dryness
  6. temperatureheated
  7. temperatureto near-reflux
  8. filtrationThe resulting solid was collected via filtration

Sources & evidence

ORD record
ord-13ebd2fa14b346388c0dab95ce6385e8
Source dataset
uspto-grants-2015_11
Patent number
US09181223B2

Reaction notes

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