Diisopropylethylamine → 1-[7-(2-Chlorophenyl)-8-iodo-2-methylpyrazolo[1,5-a][1,3,5]triazin-4-yl]-3-ethylaminoazetidine-3-carboxylic Acid Amide

HRID 2054412Notes

Reaction equation

HRID 2054412 reaction equation
[CH2:1]([NH:3][C:4]1([C:8]([NH2:10])=[O:9])[CH2:7][NH:6][CH2:5]1)[CH3:2].C(N(C(C)C)CC)(C)C.Cl[C:21]1[N:26]2[N:27]=[C:28]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=3[Cl:37])[C:29]([I:30])=[C:25]2[N:24]=[C:23]([CH3:38])[N:22]=1>CN(C=O)C.C(Cl)Cl>[Cl:37][C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=1[C:28]1[C:29]([I:30])=[C:25]2[N:24]=[C:23]([CH3:38])[N:22]=[C:21]([N:6]3[CH2:7][C:4]([NH:3][CH2:1][CH3:2])([C:8]([NH2:10])=[O:9])[CH2:5]3)[N:26]2[N:27]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 112865313-(Ethylamino)azetidine-3-carboxamideHCID 596556974-Chloro-7-(2-chlorophenyl)-8-iodo-2-methylpyrazolo[1,5-a][1,3,5]triazine

Product 1

HCID 596557281-[7-(2-Chlorophenyl)-8-iodo-2-methylpyrazolo[1,5-a][1,3,5]triazin-4-yl]-3-ethylaminoazetidine-3-carboxylic Acid Amide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-ethylaminoazetidine-3-carboxylic acid amide (I-2A-1g; 0.55 g, 2.5 mmol) and diisopropylethylamine (1.3 ml, 7.6 mmol) in DMF (10 ml) was added a solution of 4-chloro-7-(2-chlorophenyl)-8-iodo-2-methylpyrazolo[1,5-a][1,3,5]triazine (I-1A-1e; 0.93 g, 2.3 mmol) in methylene chloride (10 ml). After stirring 2 hours, the methylene chloride was removed, in vacuo, and the mixture was extracted from water, adjusted to pH 8 with saturated aqueous NaHCO3, with ethyl acetate. The combined organic layers were washed with water and brine, dried (MgSO4), and then concentrated, in vacuo, to afford a yellow solid. The material was then triturated from methylene chloride/methanol to afford I-6A-1a (0.73 g, 62%) as a colorless solid: +APcI MS (M+1) 512.0; 1H NMR (400 MHz, CDCl3) δ 7.51 (d, J=7.9 Hz, 1H), 7.43-7.34 (m, 3H), 6.99 (d, J=4.7 Hz, 1H), 5.42 (d, J=4.7 Hz, 1H), 5.24 (br d, J=9.5 Hz, 1H), 4.81 (br d, J=9.5 Hz, 1H), 4.69 (br d, J=9.5 Hz, 1H), 4.13 (br d, J=9.5 Hz, 1H), 2.68-2.58 (m, 2H), 2.54 (s, 3H), 1.16 (t, J=7.0 Hz, 3H).

Workup

  1. customthe methylene chloride was removed, in vacuo
  2. extractionthe mixture was extracted from water
  3. washThe combined organic layers were washed with water and brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated, in vacuo
  6. customto afford a yellow solid
  7. customThe material was then triturated from methylene chloride/methanol
  8. customto afford I-6A-1a (0.73 g, 62%) as a colorless solid

Sources & evidence

ORD record
ord-bd20d9143bf84ee6993ae5c91f9abd1d
Source dataset
uspto-grants-2008_02
Patent number
US07329658B2

Reaction notes

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