Isopropanol → HCID 66763496, compound

HRID 578669Notes

Reaction equation

HRID 578669 reaction equation
C[O:2][C:3]([C:5]1[CH:6]=[CH:7][CH:8]=[C:9]2[C:14]=1[N:13]=[CH:12][N:11]=[C:10]2[NH:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([NH:23][C:24]([C:26]2[CH:27]=[N:28][CH:29]=[C:30]([N:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)[CH:31]=2)=[O:25])[CH:18]=1)=O.C1COCC1.CC(O)C.[OH-].[NH4+:48]>O>[N:32]1([C:30]2[CH:31]=[C:26]([C:24]([NH:23][C:19]3[CH:18]=[C:17]([CH:22]=[CH:21][CH:20]=3)[CH2:16][NH:15][C:10]3[C:9]4[C:14](=[C:5]([C:3]([NH2:48])=[O:2])[CH:6]=[CH:7][CH:8]=4)[N:13]=[CH:12][N:11]=3)=[O:25])[CH:27]=[N:28][CH:29]=2)[CH2:33][CH2:34][O:35][CH2:36][CH2:37]1

Participants

6

Reactant 4

HCID 3776IsopropanolHCID 8028TetrahydrofuranHCID 14923Ammonium HydroxideHCID 66763860HCID 66763860, compound

Product 1

HCID 66763496HCID 66763496, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

To a 40-mL vial with magnetic stirbar at 25° C. was added 4-{3-[(5-Morpholin-4-yl-pyridine-3-carbonyl)-amino]-benzylamino}-quinazoline-8-carboxylic acid methyl ester (0.12 g, 0.24 mmol, 1 eq.) and THF (2 mL) and 2-propanol (2 mL). An approx. equal volume (i.e.; 2 mL) of concentrated aqueous ammonium hydroxide solution (28-30% soln.) was then added and stirring continued over the weekend (×96 hours). Water (15 mL) was added to the reaction mixture and a precipitate immediately began to form. The precipitate was collected and dried thoroughly in vacuo. The material required further purification via preparative HPLC. The isolated material was re-dissolved in THF (1 mL), iPrOH (1 mL), and DMSO (1 mL) to which concentrated aqueous ammonium hydroxide solution (28-30%) (1 mL) was added and heated at 50° C.×36 hours. H2O (10 mL) was added to the reaction mixture and the resulting white precipitate collected and dried thoroughly in vacuo to afford 50.2 mg (45% yield). LCMS (ESI) 484.2 (M+H).

Workup

  1. customcontinued over the weekend (×96 hours)
  2. customto form
  3. customThe precipitate was collected
  4. customdried thoroughly in vacuo
  5. customThe material required further purification via preparative HPLC
  6. dissolutionThe isolated material was re-dissolved in THF (1 mL)
  7. additioniPrOH (1 mL), and DMSO (1 mL) to which concentrated aqueous ammonium hydroxide solution (28-30%) (1 mL) was added
  8. additionH2O (10 mL) was added to the reaction mixture
  9. customthe resulting white precipitate collected
  10. customdried thoroughly in vacuo
  11. customto afford 50.2 mg (45% yield)

Sources & evidence

ORD record
ord-e2008a1096d644abbb3397aa39916498
Source dataset
uspto-grants-2015_05
Patent number
US09040560B2

Reaction notes

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