Hydrochloric Acid → HCID 53819466, compound

HRID 1594831Notes

Reaction equation

HRID 1594831 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:26]#[C:27][CH:28]4[CH2:33][CH2:32][CH2:31][NH:30][CH2:29]4)[CH:24]=3)[N:19]=[CH:18][N:17]=2)[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[CH:34](=O)[CH2:35][CH3:36].[BH3-]C#N.[Na+].Cl>CO.O.CC(O)=O>[CH3:1][C:2]1[CH:3]=[C:4]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:26]#[C:27][CH:28]4[CH2:33][CH2:32][CH2:31][N:30]([CH2:34][CH2:35][CH3:36])[CH2:29]4)[CH:24]=3)[N:19]=[CH:18][N:17]=2)[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 527PropanalHCID 5003444Sodium cyanoborohydrideHCID 18616536HCID 18616536, compound

Product 1

HCID 53819466HCID 53819466, compoundYield 44.1%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 22242641Methanol--water (1/1)Solvent

Procedure

(3-Methyl-4-phenoxy-phenyl)-(6-piperidin-3-ylethynyl-quinazolin-4-yl)-amine (114 mg, 0.2 mmol) and propionaldehyde (116 mg, 2.0 mmol) were dissolved in MeOH/H2O (5/0.5 mL) and the pH was adjusted to 5 with AcOH. The reaction was stirred at room temperature overnight and followed by the addition of NaBH3CN (13 mg, 0.2 mmol) over a period of 1 hour. After stirring for another hour, the reaction was concentrated and the residue was partitioned between CH2Cl2 (30 mL) and saturated Na2CO3 (20 mL). The separated organic layer was dried over sodium sulfate and concentrated. Purification by preparative TLC using 10% MeOH in EtOAc gave the free base product which was converted to HCl salt to yield 42 mg (38%) of yellow solid: 1H NMR (CD3OD) δ 1.03 (t, 3H), 1.78-1.87 (m, 4H), 2.01-2.08 (m, 2H), 2.28 (s, 3H), 2.96 (t, 1H), 3.07-3.19 (m, 3H), 3.31 (br, 1H), 3.59 (d, 1H), 3.80 (d, 1H), 6.94 (m, 3H), 7.09 (t, 1H), 7.34 (t, 2H), 7.53 (d, 1H), 7.63 (s, 1H), 7.80 (d, 1H), 8.05 (dd, 1H), 8.73 (s, 1H), 8.75 (s, 1H); MS m/z (MH+) 477.1.

Workup

  1. stirringAfter stirring for another hour
  2. concentrationthe reaction was concentrated
  3. customthe residue was partitioned between CH2Cl2 (30 mL) and saturated Na2CO3 (20 mL)
  4. dry with materialThe separated organic layer was dried over sodium sulfate
  5. concentrationconcentrated
  6. customPurification by preparative TLC
  7. customgave the free base product which

Sources & evidence

ORD record
ord-c2ac423850ff4cbab6b3f4adaa0470d8
Source dataset
uspto-grants-2001_09
Patent number
US06284764B1

Reaction notes

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