Ammonium Hydroxide → 4-[4-(3-Amino-2-fluorophenyl)-2-(1,1-dimethylethyl)-1,3-thiazol-5-yl]-2-pyrimidinamine

HRID 239368Notes

Reaction equation

HRID 239368 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([C:13]([CH3:16])([CH3:15])[CH3:14])=[N:10][C:9]=2[C:17]2[C:18]([F:24])=[C:19]([CH:21]=[CH:22][CH:23]=2)[NH2:20])[CH:5]=[CH:4][N:3]=1.[NH4+:25].[OH-].O1CCOCC1>O>[NH2:20][C:19]1[C:18]([F:24])=[C:17]([C:9]2[N:10]=[C:11]([C:13]([CH3:16])([CH3:15])[CH3:14])[S:12][C:8]=2[C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH2:25])[N:7]=2)[CH:23]=[CH:22][CH:21]=1

Participants

5

Reactant 3

HCID 14923Ammonium HydroxideHCID 312751,4-DioxaneHCID 579898453-(2-Tert-butyl-5-(2-chloropyrimidin-4-yl)thiazol-4-yl)-2-fluoroaniline

Product 1

HCID 579897094-[4-(3-Amino-2-fluorophenyl)-2-(1,1-dimethylethyl)-1,3-thiazol-5-yl]-2-pyrimidinamineYield 83.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
130 °C

Procedure

In a microwave reaction vessel 3-[5-(2-chloro-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-2-fluoroaniline (590 mg, 1.626 mmol) was combined with NH4OH 28-30% (15 mL, 385 mmol) and 1,4-dioxane (4 mL). The mixture was heated in the microwave for 40 min at 130° C. The crude product was then diluted with water (100 mL) followed by extraction with EtOAc (100 mL). The EtOAc layer was washed with brine then dried over Na2SO4. The organics were then filtered and concentrated to dryness. The crude material was dissolved in DCM (2 mL), injected onto the top of a silica gel column then purified using EtOAc and hexanes. Desired fractions were concentrated to dryness to yield the title compound of Step A as a beige powder (490 mg, 1.355 mmol, 83% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.06 (d, J=5.1 Hz, 1H), 6.97 (t, J=7.8 Hz, 1H), 6.86 (t, J=8.2 Hz, 1H), 6.71 (s, 2H), 6.58 (t, J=6.2 Hz, 1H), 6.15 (d, J=5.1 Hz, 1H), 5.26 (s, 2H), 1.42 (s, 9H).

Workup

  1. extractionfollowed by extraction with EtOAc (100 mL)
  2. washThe EtOAc layer was washed with brine
  3. dry with materialthen dried over Na2SO4
  4. filtrationThe organics were then filtered
  5. concentrationconcentrated to dryness
  6. dissolutionThe crude material was dissolved in DCM (2 mL)
  7. customthen purified
  8. concentrationDesired fractions were concentrated to dryness

Sources & evidence

ORD record
ord-6f128014553e4b3e972e1526f9d438b0
Source dataset
uspto-grants-2014_02
Patent number
US08642759B2

Reaction notes

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