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Triethylamine → {3-[1-(3-Benzyl-4-oxo-3,4-dihydro-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-propylamino]-propyl}-carbamic acid tert-butyl ester

HRID 1795945
Notes
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Reaction equation

HRID 1795945 reaction equation
[CH2:1]([N:8]1[C:13](=[O:14])[C:12]2=[CH:15][CH:16]=[CH:17][N:11]2[N:10]=[C:9]1[CH:18](O)[CH2:19][CH3:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.CS(Cl)(=O)=O.S([O-])(=O)(=O)C.[C:39]([NH:46][CH2:47][CH2:48][CH2:49][NH2:50])([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40]>C(Cl)Cl.C([O-])(O)=O.[Na+].CCOC(C)=O.CN1C(=O)CCC1.O>[C:42]([O:41][C:39](=[O:40])[NH:46][CH2:47][CH2:48][CH2:49][NH:50][CH:18]([C:9]1[N:8]([CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[C:13](=[O:14])[C:12]2=[CH:15][CH:16]=[CH:17][N:11]2[N:10]=1)[CH2:19][CH3:20])([CH3:45])([CH3:43])[CH3:44]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

11

Reactant 5

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 85257MethanesulfonateHCID 2735700tert-Butyl (3-aminopropyl)carbamateHCID 22180024(+/-)-3-Benzyl-2-(1-hydroxy-propyl)-3H-pyrrolo[2,1-f][1,2,4]triazin-4-one

Product 1

HCID 21025743
{3-[1-(3-Benzyl-4-oxo-3,4-dihydro-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-propylamino]-propyl}-carbamic acid tert-butyl ester
Yield 61%

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of (±)-3-benzyl-2-(1-hydroxy-propyl)-3H-pyrrolo[2,1-f][1,2,4]triazin-4-one (0.70 g, 2.47 mmol) in methylene chloride (20 mL) at 0° C. was added triethylamine (517 μL, 3.71 mmol) followed by methanesulfonyl chloride (290 μL, 3.71 mmol). The reaction was stirred at room temperature for 45 min and was then diluted methylene chloride (10 mL) and water (10 mL). The layers were separated and the aqueous layer was extracted with methylene chloride (10 mL). The combined organic extracts were washed with brine (10 mL), dried over anhydrous MgSO4, and concentrated in vacuo. The crude mesylate was treated with N-BOC-1,3-diaminopropane (Fluka, 1.29 g, 7.41 mmol) and NMP (20 mL) at 75° C. for 14 h. After cooling to room temperature, the reaction was diluted with saturated NaHCO3 solution (30 mL) and EtOAc (30 mL). The layers were separated and the aqueous layer was extracted with EtOAc (2×30 mL). The combined organic extracts were washed with 10% LiCl solution (30 mL), dried over anhydrous MgSO4, and concentrated in vacuo. Purification of the crude product by flash column chromatography (SiO2, EtOAc/Hexane 1:1) gave the title compound as a colorless viscous oil (610 mg, 61%): 1H NMR (CDCl3) δ 7.25 (m, 6H), 7.01 (m, 1H), 6.47 (m, 1H), 5.66 (d, 1H, J=16.2 Hz), 5.04 (brs, 1H), 4.85 (d, 1H, J=16.1 Hz), 3.48 (m, 1H), 2.91 (m, 2H), 2.42 (m, 1H), 1.96 (m, 1H), 1.64 (m, 2H), 1.34 (s, 9H), 1.28 (m, 2H), 0.86 (t, 3H, J=7.28 Hz); 13C NMR (CDCl3) δ 156.3, 155.7, 151.6, 137.1, 129.4, 128.1, 126.8, 121.3, 118.4, 111.2, 109.2, 79.3, 59.9, 45.8, 44.5, 39.7, 29.8, 28.8, 28.6, 11.2; MS (ESI+) 440.29 (M++H).

Workup

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted with methylene chloride (10 mL)
  3. washThe combined organic extracts were washed with brine (10 mL)
  4. dry with materialdried over anhydrous MgSO4
  5. concentrationconcentrated in vacuo
  6. temperatureAfter cooling to room temperature
  7. customThe layers were separated
  8. extractionthe aqueous layer was extracted with EtOAc (2×30 mL)
  9. washThe combined organic extracts were washed with 10% LiCl solution (30 mL)
  10. dry with materialdried over anhydrous MgSO4
  11. concentrationconcentrated in vacuo
  12. customPurification of the crude product by flash column chromatography (SiO2, EtOAc/Hexane 1:1)

Sources & evidence

ORD record
ord-3493b9ba56254648a70eb40fe43da435
Source dataset
uspto-grants-2006_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07030118B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes