Hydrochloric Acid → HCID 54065044, compound

HRID 1594832Notes

Reaction equation

HRID 1594832 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.O=[CH:35][CH2:36][NH:37]C(=O)OC(C)(C)C.[BH3-]C#N.[Na+].Cl>CO.O.CO.CC(O)=O>[NH2:37][CH2:36][CH2:35][N:30]1[CH2:31][CH2:32][CH2:33][CH:28]([C:27]#[C:26][C:23]2[CH:24]=[C:25]3[C:20](=[CH:21][CH:22]=2)[N:19]=[CH:18][N:17]=[C:16]3[NH:15][C:4]2[CH:5]=[CH:6][C:7]([O:8][C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)=[C:2]([CH3:1])[CH:3]=2)[CH2:29]1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 4247255tert-butyl N-(2-oxoethyl)carbamateHCID 5003444Sodium cyanoborohydrideHCID 18616536HCID 18616536, compound

Product 1

HCID 54065044HCID 54065044, compoundYield 86.9%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 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 tert-butyl N-(2-oxoethyl)carbamate (320 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 silica gel column using 5% MeOH in EtOAc gave the free base which was dissolved in MeOH. HCl gas was passed through the solution for 5 min and the deprotected product precipitated as HCl salt The mixture was diluted with EtOAc and the solid was collected by suction filtraton, rinsed with EtOAc, and further dried to afford 83 mg (71%) of yellow solid: 1H NMR (CD3OD) δ 1.71-1.82 (br, 2H), 2.0-2.12 (br, 2H), 2.27 (s, 3H), 3.00 (t, 1H), 3.03-3.19 (br, 2H), 3.40 (br, 1H), 3.50 (s, 2H), 3.62 (br d, 1H), 3.70 (m, 1H), 3.89 (br d, 1H), 6.93 (m, 3H), 7.08 (t, 1H), 7.33 (t, 2H), 7.52 (d, 1H), 7.64 (s, 1H), 7.79 (d, 1H), 8.05 (d, 1H), 8.75 (s, 1H), 8.77 (s, 1H); MS m/z (MH+) 476.1.

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 silica gel column
  7. customgave the free base which
  8. customthe deprotected product precipitated as HCl salt The mixture
  9. additionwas diluted with EtOAc
  10. customthe solid was collected by suction filtraton
  11. washrinsed with EtOAc
  12. customfurther dried

Sources & evidence

ORD record
ord-328c2fd5cae5431f88ef2c8762f82901
Source dataset
uspto-grants-2001_09
Patent number
US06284764B1

Reaction notes

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