Methanol → HCID 46893523, compound

HRID 1801964Notes

Reaction equation

HRID 1801964 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:12]2[N:21]=[C:20]([NH:22][C:23]3[CH:27]=[C:26]([CH3:28])[NH:25][N:24]=3)[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[N:13]=2)[CH2:9][C:10]#[N:11])=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].[OH-].[Na+].CO>C1COCC1.CS(C)=O.CC(O)=O>[NH2:11][CH2:10][CH2:9][CH:8]([C:12]1[N:21]=[C:20]([NH:22][C:23]2[CH:27]=[C:26]([CH3:28])[NH:25][N:24]=2)[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[N:13]=1)[C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=1

Participants

8

Reactant 4

HCID 887MethanolHCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydride2×HCID 46893520HCID 46893520, compound

Product 1

HCID 46893523HCID 46893523, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 679Dimethyl SulfoxideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To 3-(4-fluorophenyl)-3-(4-(5-methyl-1H-pyrazol-3-ylamino)quinazolin-2-yl)propanenitrile from Example 68 (80 mg, 0.21 mmol) in THF (3 mL) at 0° C. was added lithium aluminum hydride (20 mg) and the mixture was stirred for 5 min, then allowed to warm to rt and stir for 2-3 h. An additional amount of lithium aluminum hydride (40 mg) was then added and stirring was continued for 45 min. To the solution was slowly added 1 N NaOH (0.5 mL) followed by MeOH (2 mL). The mixture was stirred for 5 min and then AcOH (0.5 mL) was added, followed by DMSO (2 mL). The resulting solution was purified by preparative HPLC (Varian Diphenyl reverse phase column, eluting with a gradient of solvent B=0.05% HOAc/ACN and solvent A=0.05% HOAc/H2O) to afford 2-(3-amino-1-(4-fluorophenyl)propyl)-N-(5-methyl-1H-pyrazol-3-yl)quinazolin-4-amine as the acetate salt (21 mg, 25%). 1H NMR (300 MHz, DMSO-d6) δ 1.81 (s, 3H) 2.2-2.6 (m, 7H) 4.26 (t, 1H) 6.46 (s, 1H) 7.12 (t, 2H) 7.46-7.51 (m, 3H) 7.73-7.78 (m, 2H) 8.57 (d, 1H); LC-MS (ESI) m/z 377 (M+H)+.

Workup

  1. stirringstir for 2-3 h
  2. stirringstirring
  3. waitwas continued for 45 min
  4. stirringThe mixture was stirred for 5 min
  5. customThe resulting solution was purified by preparative HPLC (Varian Diphenyl reverse phase column
  6. washeluting with a gradient of solvent B=0.05% HOAc/ACN and solvent A=0.05% HOAc/H2O)

Sources & evidence

ORD record
ord-b1f5ed361f6749fc872a39e7995cfd1c
Source dataset
uspto-grants-2013_01
Patent number
US08349851B2

Reaction notes

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