Triethylamine → HCID 178419999, compound

HRID 707301Notes

Reaction equation

HRID 707301 reaction equation
[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[N:3][C:2]=1[NH:11][C@H:12]1[CH2:15][C@H:14]([NH:16][C:17]2[C:22]([NH2:23])=[CH:21][N:20]=[CH:19][N:18]=2)[CH2:13]1.C(N(CC)CC)C.[CH:31]1([C:34](Cl)=O)[CH2:33][CH2:32]1>O1CCCC1>[CH:31]1([C:34]2[N:16]([C@H:14]3[CH2:15][C@H:12]([NH:11][C:2]4[N:3]=[CH:4][C:5]5[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=5)[N:1]=4)[CH2:13]3)[C:17]3[C:22]([N:23]=2)=[CH:21][N:20]=[CH:19][N:18]=3)[CH2:33][CH2:32]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 77637Cyclopropanecarbonyl chlorideHCID 178508035HCID 178508035, compound

Product 1

HCID 178419999HCID 178419999, compoundYield 47.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

N4-(Trans-3-(quinazolin-2-ylamino)cyclobutyl)pyrimidine-4,5-diamine (0.045 g, 0.146 mmol) and triethylamine (0.50 ml, 3.59 mmol) were dissolved in dry tetrahydrofuran (10 mL) and treated with cyclopropanecarbonyl chloride (0.050 ml, 0.546 mmol). The reaction was stirred at room temperature for 14 hours. The mixture was evaporated to dryness under reduced pressure and the residue dissolved in acetic acid (20 mL). It was sealed in a microwave vessel and heated at 125° C. for 20 minutes then to 145° C. for 1 hour. The solution was evaporated to dryness under reduced pressure. Purification using silica chromatography (0-4% methanol in dichloromethane gradient) gave the desired N-(trans-3-(8-cyclopropyl-9H-purin-9-yl)cyclobutyl)quinazolin-2-amine (0.025 g, 0.070 mmol, 47.8% yield). M+1: 358.1. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.15-1.24 (m, 2 H) 1.24-1.33 (m, 2 H) 2.02-2.12 (m, 1 H) 2.69-2.80 (m, 2 H) 3.68-3.81 (m, 2 H) 4.89 (m, J=7.70, 7.70, 4.10 Hz, 1 H) 5.54 (quin, J=8.36 Hz, 1 H) 5.92 (br. s, 1 H) 7.23-7.35 (m, 1 H) 7.59-7.67 (m, 1 H) 7.67-7.76 (m, 2 H) 8.95 (s, 1 H) 8.91 (s, 1 H) 9.03 (s, 1 H).

Workup

  1. customThe mixture was evaporated to dryness under reduced pressure
  2. dissolutionthe residue dissolved in acetic acid (20 mL)
  3. customIt was sealed in a microwave vessel
  4. temperatureheated at 125° C. for 20 minutes
  5. waitto 145° C. for 1 hour
  6. customThe solution was evaporated to dryness under reduced pressure
  7. customPurification

Sources & evidence

ORD record
ord-766e2df40be147afb5e696aa9be6cb3b
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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