Water → Tucatinib

HRID 1753782Notes

Reaction equation

HRID 1753782 reaction equation
[N:1]1[CH:2]=[N:3][N:4]2[CH:9]=[CH:8][C:7]([O:10][C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]4[C:27]5[C:22](=[CH:23][CH:24]=[C:25]([NH:28][C:29]([NH:31][C:32]([CH3:36])([CH3:35])[CH2:33][OH:34])=S)[CH:26]=5)[N:21]=[CH:20][N:19]=4)=[CH:13][C:12]=3[CH3:37])=[CH:6][C:5]=12.O>C1COCC1>[N:1]1[CH:2]=[N:3][N:4]2[CH:9]=[CH:8][C:7]([O:10][C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]4[C:27]5[C:22](=[CH:23][CH:24]=[C:25]([NH:28][C:29]6[O:34][CH2:33][C:32]([CH3:36])([CH3:35])[N:31]=6)[CH:26]=5)[N:21]=[CH:20][N:19]=4)=[CH:13][C:12]=3[CH3:37])=[CH:6][C:5]=12

Participants

4

Reactant 2

HCID 962WaterHCID 86731560Tucatinib N-1

Product 1

HCID 51039094Tucatinib

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

N4-(4-([1,2,4]Triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine was synthesized from 1-(4-((4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)amino)quinazolin-6-yl)-3-(1-hydroxy-2-methylpropan-2-yl)thiourea (322 g) in THF (3 L) at 0° C. Water (10 L) was added, and the solution was allowed to stir for 1 hour, at which point the material oiled out. The organics were then extracted into ethyl acetate (3×5000 mL), combined and washed with water (2×5000 mL) and brine (2×5000 mL). The organics were dried by rotoevaporation, and the material was concentrated to an oil. The oil was observed to solidify at room temperature to yield Form E.

Workup

  1. extractionThe organics were then extracted into ethyl acetate (3×5000 mL)
  2. washwashed with water (2×5000 mL) and brine (2×5000 mL)
  3. customThe organics were dried by rotoevaporation
  4. concentrationthe material was concentrated to an oil
  5. customto solidify at room temperature
  6. customto yield Form E

Sources & evidence

ORD record
ord-a06dcf4a8c1b42159914bef70670ff3f
Source dataset
uspto-grants-2015_10
Patent number
US09168254B2

Reaction notes

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