Triethylamine → N-[4-(4-amino-7-[3-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]propyl}pyrrolo[2,1-f][1,2,4]triazin-5-yl)-2-fluorophenyl]-N'-[2-fluoro-5-(trifluoromethyl)phenyl]urea

HRID 1091503Notes

Reaction equation

HRID 1091503 reaction equation
[NH2:1][C:2]1[C:7]2=[C:8]([C:15]3[CH:20]=[CH:19][C:18]([NH:21][C:22]([NH:24][C:25]4[CH:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=[CH:27][C:26]=4[F:35])=[O:23])=[C:17]([F:36])[CH:16]=3)[CH:9]=[C:10]([CH2:11][CH2:12][CH2:13]Br)[N:6]2[N:5]=[CH:4][N:3]=1.[CH3:37][O:38][CH2:39][C@@H:40]1[CH2:44][CH2:43][CH2:42][NH:41]1.C(N(CC)CC)C>CN(C=O)C>[NH2:1][C:2]1[C:7]2=[C:8]([C:15]3[CH:20]=[CH:19][C:18]([NH:21][C:22]([NH:24][C:25]4[CH:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=[CH:27][C:26]=4[F:35])=[O:23])=[C:17]([F:36])[CH:16]=3)[CH:9]=[C:10]([CH2:11][CH2:12][CH2:13][N:41]3[CH2:42][CH2:43][CH2:44][C@H:40]3[CH2:39][O:38][CH3:37])[N:6]2[N:5]=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 671217(S)-(+)-2-(Methoxymethyl)pyrrolidineHCID 592319471-{4-[4-Amino-7-(3-bromopropyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]-2-fluorophenyl}-3-[2-fluoro-5-(trifluoromethyl)phenyl]urea

Product 1

HCID 17751774N-[4-(4-amino-7-[3-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]propyl}pyrrolo[2,1-f][1,2,4]triazin-5-yl)-2-fluorophenyl]-N'-[2-fluoro-5-(trifluoromethyl)phenyl]ureaYield 65.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
55 °C

Procedure

1-{4-[4-amino-7-(3-bromopropyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]-2-fluorophenyl}-3-[2-fluoro-5-(trifluoromethyl)phenyl]urea (Example 193 step 1) (50 mg, 0.088 mmol) and (2S)-2-(methoxymethyl)pyrrolidine (36 uL, 0.263 mmol) were added to a vial. DMF was added (1 mL) followed by triethylamine (15 uL, 0.109 mmol) and KI (spatula tip). The vial was capped and the reaction heated at 55° C. for two hours. Upon cooling the product precipitated out of solution. The solids were collected by filtration and rinsed with ether to yield 35 mg (65%) of clean product. 1H-NMR (DMSO-d6) δ 9.41 (s, 1H), 9.25 (s, 1H), 8.65 (d, J=7.2 Hz, 1H), 8.26 (t, J=8.4 Hz, 1H), 7.89 (s, 1H), 7.55 to 7.21 (m, 4H), 6.57 (s, 1H), 3.32 (s, 3H), 3.18 to 2.83 (m, 7H), 2.37 to 1.45 (m, 5H); MS [M+H]+=604.2; LCMS RT=2.59

Workup

  1. customThe vial was capped
  2. temperatureUpon cooling the product
  3. customprecipitated out of solution
  4. filtrationThe solids were collected by filtration
  5. washrinsed with ether

Sources & evidence

ORD record
ord-61e682bd6d7645aea5567c90147ba051
Source dataset
uspto-grants-2012_03
Patent number
US08129379B2

Reaction notes

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