Triethylamine → HCID 58529878, compound

HRID 1972834Notes

Reaction equation

HRID 1972834 reaction equation
[CH2:1]([N:8]1[CH:16]=[C:15]2[C:10]([CH:11]=[C:12]([C:17]3[CH:18]=[C:19]([CH:27]4[CH2:31][CH2:30][NH:29][CH2:28]4)[N:20]4[C:25]=3[C:24]([NH2:26])=[N:23][CH:22]=[N:21]4)[CH:13]=[CH:14]2)=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:32]([O:36][C:37]([N:39]1[CH2:42][CH:41]([C:43](O)=[O:44])[CH2:40]1)=[O:38])([CH3:35])([CH3:34])[CH3:33].C(N(CC)CC)C>CN(C=O)C>[NH2:26][C:24]1[C:25]2=[C:17]([C:12]3[CH:13]=[CH:14][C:15]4[C:10]([CH:11]=3)=[N:9][N:8]([CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH:16]=4)[CH:18]=[C:19]([CH:27]3[CH2:31][CH2:30][N:29]([C:43]([CH:41]4[CH2:42][N:39]([C:37]([O:36][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:38])[CH2:40]4)=[O:44])[CH2:28]3)[N:20]2[N:21]=[CH:22][N:23]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 27559811-Boc-Azetidine-3-carboxylic acidHCID 58529326HCID 58529326, compound

Product 1

HCID 58529878HCID 58529878, compoundYield 35%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (5-(2-benzyl-2H-indazol-6-yl)-7-pyrrolidin-3-ylpyrrolo[2,1-f][1,2,4]triazin-4-amine (100 mg, 0.244 mmol) in DMF (1.5 mL) was added 1-(tert-butoxycarbonyl)azetidine-3-carboxylic acid (50.6 mg, 0.252 mmol), triethylamine (102 μl, 0.733 mmol), and (BOP) benzoltriazolyloxytris(dimethylamino)phosphomium-hexafluorophosphate (140 mg, 0.317 mmol). The reaction was stirred at rt overnight. The mixture was partitioned between ethyl acetate (25 mL) and H2O (25 mL). The layers were separated and the organic was washed with H2O (20 mL). The combined aqueous layers were extracted with ethyl acetate (20 mL). The combined organics were washed with water (5×20 mL) to remove DMF, dried (Na2SO4), and evaporated. The crude material was purified by trituration with ether to yield 50 mg (35%) of the desired product. 1H NMR (300 MHz, Methanol-d6) δ 8.36 (s, 1 H), 7.85-7.81 (m, 2 H), 7.65 (s, 1 H), 7.40-7.20 (m, 4 H), 7.23 (d, 1 H), 6.67 (d, 1 H), 5.85 (s, 2 H), 4.20-3.90 (m, 3 H), 3.80-3.40 (m, 2 H), 3.30-3.10 (m, 4 H), 2.60-2.10 (m, 2 H), 1.33 (d, 9H); ES-MS m/z 579.0 [M+H]+, HPLC RT (min) 2.46.

Workup

  1. customThe mixture was partitioned between ethyl acetate (25 mL) and H2O (25 mL)
  2. customThe layers were separated
  3. washthe organic was washed with H2O (20 mL)
  4. extractionThe combined aqueous layers were extracted with ethyl acetate (20 mL)
  5. washThe combined organics were washed with water (5×20 mL)
  6. customto remove DMF
  7. dry with materialdried (Na2SO4)
  8. customevaporated
  9. customThe crude material was purified by trituration with ether

Sources & evidence

ORD record
ord-f1d0c88efd0f4c79b58aefc6f7db3106
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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