Dimethylformamide → neopentyl((S)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-yl)methylcarbamate

HRID 2079437Notes

Reaction equation

HRID 2079437 reaction equation
[NH2:1][CH2:2][C@@H:3]1[CH2:7][CH2:6][N:5]([C:8]2[C:17]3[C:12](=[CH:13][C:14]([CH3:18])=[CH:15][CH:16]=3)[N:11]=[C:10]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[OH:25])[N:9]=2)[CH2:4]1.CN(C=O)C.C(N(CC)CC)C.Cl[C:39]([O:41][CH2:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:40]>C(Cl)Cl>[OH:25][C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=1[C:10]1[N:9]=[C:8]([N:5]2[CH2:6][CH2:7][C@@H:3]([CH2:2][NH:1][C:39](=[O:40])[O:41][CH2:42][C:43]([CH3:46])([CH3:45])[CH3:44])[CH2:4]2)[C:17]2[C:12](=[CH:13][C:14]([CH3:18])=[CH:15][CH:16]=2)[N:11]=1

Participants

6

Reactant 4

HCID 6228Dimethylformamide2×HCID 8471TriethylamineHCID 33521852,2-Dimethylpropyl carbonochloridateHCID 1361213492-(4-((S)-3-(aminomethyl)pyrrolidin-1-yl)-7-methylquinazolin-2-yl)phenol

Product 1

HCID 136121466neopentyl((S)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-yl)methylcarbamateYield 94%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-(4-((S)-3-(aminomethyl)pyrrolidin-1-yl)-7-methylquinazolin-2-yl)phenol (200 mg, 0.6 mmol), DMF (6.0 mL), and DMF (1 mL) was stirred under an N2 atmosphere. Triethylamine (0.166 mL, 1.2 mmol) was added, and the reaction was cooled in an ice bath. To this was added 1 M neopentyl chloroformate solution (89 μL in 600 μL THF, 0.6 mmol). After allowing the reaction mixture to warm to room temperature over a period of 30 minutes, CH2Cl2 was added to the reaction mixture, and it was washed once with water before it was dried over Na2SO4, filtered, and concentrated. Purification via silica gel chromatography using 0-20% EtOAc in CH2Cl2/hexanes (1:1) gave neopentyl ((S)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-yl)methylcarbamate (222 mg, 94%). LC/MS: m/z 449 (M+H)+ at 2.73 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)). 1H NMR (400 MHz, acetic acid-d4) δ 8.42 (dd, J=8.1, 1.8 Hz, 1H), 8.20 (d, J=8.7 Hz, 1H), 7.57 (s, 1H), 7.40-7.29 (m, 3H), 6.92-6.89 (m, 2H), 4.11-3.92 (m, 3H), 3.78-3.61 (m, 3H), 3.33-3.28 (m, 1H), 3.23-3.10 (m, 2H), 2.49 (s, 3H), 2.16-2.08 (m, 1H), 1.83-1.75 (m, 1H), 0.89 (s, 9H) ppm.

Workup

  1. temperaturethe reaction was cooled in an ice bath
  2. washwas washed once with water before it
  3. dry with materialwas dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification via silica gel chromatography

Sources & evidence

ORD record
ord-1bb9359348c44fda8557ae775a0b1c2b
Source dataset
uspto-grants-2011_04
Patent number
US07928107B2

Reaction notes

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