Triethylamine → Tert-butyl 4-(6-fluoroquinazolin-2-yl)-6,7-dimethyl-1,4-diazepane-1-carboxylate

HRID 1808917Notes

Reaction equation

HRID 1808917 reaction equation
[CH3:1][CH:2]1[CH:8]([CH3:9])[N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5][NH:4][CH2:3]1.Cl[C:18]1[N:27]=[CH:26][C:25]2[C:20](=[CH:21][CH:22]=[C:23]([F:28])[CH:24]=2)[N:19]=1.C(N(CC)CC)C>CN(C=O)C.CCOC(C)=O>[F:28][C:23]1[CH:24]=[C:25]2[C:20](=[CH:21][CH:22]=1)[N:19]=[C:18]([N:4]1[CH2:3][CH:2]([CH3:1])[CH:8]([CH3:9])[N:7]([C:10]([O:12][C:13]([CH3:14])([CH3:16])[CH3:15])=[O:11])[CH2:6][CH2:5]1)[N:27]=[CH:26]2

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 179135522-Chloro-6-fluoroquinazolineHCID 59527658Tert-butyl 6,7-dimethyl-1,4-diazepane-1-carboxylate

Product 1

HCID 59527664Tert-butyl 4-(6-fluoroquinazolin-2-yl)-6,7-dimethyl-1,4-diazepane-1-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
130 °C

Procedure

The amine 1-4 (270 mg, 1.18 mmol) was combined with 2-chloro-6-fluoroquinazoline 1-8 (216 mg, 1.18 mmol; see example 1-D), and triethylamine (412 uL, 2.96 mmol), in DMF (5 mL) and heated to 130° C. for 3 hours. The reaction was diluted with EtOAc, washed with saturated sodium bicarbonate solution and brine and the organic layer concentrated in vacuo and the residue was purified by column chromatography on silica gel (0 to 100% EtOAc in hexanes) to provide 1-10. Data for 1-10: LC/MS: m/z (M+Na)=375.2 found; 375.4 calculated.

Workup

  1. washwashed with saturated sodium bicarbonate solution and brine
  2. concentrationthe organic layer concentrated in vacuo
  3. customthe residue was purified by column chromatography on silica gel (0 to 100% EtOAc in hexanes)
  4. customto provide 1-10

Sources & evidence

ORD record
ord-060cf47e2cbb40c3b8777aa9cb31524b
Source dataset
uspto-grants-2013_01
Patent number
US08362009B2

Reaction notes

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