tert-Butyl (3-aminopropyl)carbamate → (3-{[(3-Benzyl-5-chloro-4-oxo-3,4-dihydro-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-cyclopropyl-methyl]-amino}-propyl)-carbamic acid tert-butyl ester

HRID 1795979Notes

Reaction equation

HRID 1795979 reaction equation
[C:1]([O:5][C:6](=[O:12])[NH:7][CH2:8][CH2:9][CH2:10][NH2:11])([CH3:4])([CH3:3])[CH3:2].[CH2:13]([N:20]1[C:25](=[O:26])[C:24]2=[C:27]([Cl:30])[CH:28]=[CH:29][N:23]2[N:22]=[C:21]1[CH:31](Cl)[CH:32]1[CH2:34][CH2:33]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>CN1C(=O)CCC1>[C:1]([O:5][C:6](=[O:12])[NH:7][CH2:8][CH2:9][CH2:10][NH:11][CH:31]([C:21]1[N:20]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:25](=[O:26])[C:24]2=[C:27]([Cl:30])[CH:28]=[CH:29][N:23]2[N:22]=1)[CH:32]1[CH2:33][CH2:34]1)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 2735700tert-Butyl (3-aminopropyl)carbamateHCID 221800283-benzyl-5-chloro-2-(chloro-cyclopropyl-methyl)-3H-pyrrolo[2,1-f][1,2,4]triazin-4-one

Product 1

HCID 69591847(3-{[(3-Benzyl-5-chloro-4-oxo-3,4-dihydro-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-cyclopropyl-methyl]-amino}-propyl)-carbamic acid tert-butyl esterYield 81%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
100 °C

Procedure

(3-Amino-propyl)-carbamic acid tert-butyl ester (Fluka, 0.527 mL, 3.02 mmol) was added to a solution of 3-benzyl-5-chloro-2-(chloro-cyclopropyl-methyl)-3H-pyrrolo[2,1-f][1,2,4]triazin-4-one (0.35 g, 1.01 mmol) in NMP (3.3 mL) at room temperature. The reaction mixture was degassed with N2 and then stirred at 100° C. for 12 h. The reaction mixture was cooled to room temperature and the crude product was purified by loading directly onto a reverse phase C-18 HPLC with a 30 min gradient eluting with 45–90% aqueous methanol with 0.1% TFA to afford the title compound (0.397 g, 81%) as a solid: 1H NMR (DMF-d7) 7.74 (m, 1H), 7.35–7.49 (m, 5H), 6.85 (m, 2H), 5.85 (m, 1H), 5.45 (m, 1H), 3.15–3.25 (m, 3H), 2.70–2.85 (m, 2H), 2.55 (br m, 1H), 1.55–165 (m, 2H), 1.47 (s, 9H), 1.40 (br m, 1H), 0.65–0.75 (m, 1H), 0.41–0.46 (m, 2H), 0.15 (br m, 1H); MS (ESI+) 486 (M++H); HRMS (ESI+) calculated: 486.2272 (M++H). found: 486.2256 (M++H).

Workup

  1. customThe reaction mixture was degassed with N2
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customthe crude product was purified by loading directly onto a reverse phase C-18 HPLC with a 30 min
  4. washgradient eluting with 45–90% aqueous methanol with 0.1% TFA

Sources & evidence

ORD record
ord-fe5e5fc8acfa49eb96a7e1182d4e2925
Source dataset
uspto-grants-2006_04
Patent number
US07030118B2

Reaction notes

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