Ammonia → 4-(5-(6-(4-Methylpyridin-2-ylamino)pyridin-2-yl)thiazol-2-yl)benzamide

HRID 1854627Notes

Reaction equation

HRID 1854627 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]2[N:14]=[C:13]([C:15]3[S:19][C:18]([C:20]4[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[CH:22][CH:21]=4)=[N:17][CH:16]=3)[CH:12]=[CH:11][CH:10]=2)[CH:3]=1.N.[OH:29]O>CCO>[CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]2[N:14]=[C:13]([C:15]3[S:19][C:18]([C:20]4[CH:27]=[CH:26][C:23]([C:24]([NH2:25])=[O:29])=[CH:22][CH:21]=4)=[N:17][CH:16]=3)[CH:12]=[CH:11][CH:10]=2)[CH:3]=1

Participants

5

Reactant 3

HCID 222Ammonia2×HCID 784Hydrogen Peroxide2×HCID 533122454-(5-(6-(4-Methylpyridin-2-ylamino)pyridin-2-yl)thiazol-2-yl)benzonitrile

Product 1

HCID 533122444-(5-(6-(4-Methylpyridin-2-ylamino)pyridin-2-yl)thiazol-2-yl)benzamide

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
40 °C

Procedure

4-(5-(6-(4-methylpyridin-2-ylamino)pyridin-2-yl)thiazol-2-yl)benzonitrile (Example 51, 40 mg, 0.11 mmol) was suspended in EtOH (8 ml). Aqueous ammonia (28-30%, 4 ml) was added followed by H2O2 (35%, 1 ml). The reaction mixture was stirred at 40° C. for 2.5 days. Aqueous ammonia (2 ml) and H2O2 (0.250 ml) were added and the reaction mixture was stirred a further 24 hours at 40° C. The reaction was partitioned between H2O (30 ml) and EtOAc (70 ml). After separation, the aqueous phase was extracted again with EtOAc (70 ml). After evaporation, and purification of the crude product by dry flash chromatography over SiO2 eluting with EtOAc/MeOH (5%-10%)/NEt3 (0.5%), 4-(5-(6-(4-methylpyridin-2-ylamino)pyridin-2-yl)thiazol-2-yl)benzamide was obtained as a yellow solid (46 mg, 74%). 1H NMR (300 MHz, DMSO-d6) δ 9.72 (br s, 1H), 8.59 (br s, 1H), 8.20-7.98 (m, 6H), 7.95 (d, J=8.6 Hz, 1H), 7.78-7.70 (m, 1H), 7.66 (d, J=8.8 Hz, 1H), 7.57-7.45 (m, 3H), 2.25 (s, 3H). (APCI+) m/z 388 (M+H)+.

Workup

  1. stirringthe reaction mixture was stirred a further 24 hours at 40° C
  2. customThe reaction was partitioned between H2O (30 ml) and EtOAc (70 ml)
  3. customAfter separation
  4. extractionthe aqueous phase was extracted again with EtOAc (70 ml)
  5. customAfter evaporation, and purification of the crude product
  6. dry with materialby dry flash chromatography over SiO2 eluting with EtOAc/MeOH (5%-10%)/NEt3 (0.5%)

Sources & evidence

ORD record
ord-2218a6f3b4994d40afa1942ead821c10
Source dataset
uspto-grants-2015_02
Patent number
US08962665B2

Reaction notes

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