Azetidine → 1-[2-(2-Chlorophenyl)-3-iodopyrazolo[1,5-a]pyrimidin-7-yl]-3-ethylaminoazetidine-3-carboxylic Acid Amide

HRID 348027Notes

Reaction equation

HRID 348027 reaction equation
Cl.[CH2:2]([NH:4][C:5]1([C:9]([NH2:11])=[O:10])[CH2:8][NH:7][CH2:6]1)[CH3:3].C(N(C(C)C)CC)(C)C.Cl[C:22]1[N:27]2[N:28]=[C:29]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=3[Cl:38])[C:30]([I:31])=[C:26]2[N:25]=[CH:24][CH:23]=1.N1CCC1>CC(C)=O>[Cl:38][C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][C:32]=1[C:29]1[C:30]([I:31])=[C:26]2[N:25]=[CH:24][CH:23]=[C:22]([N:7]3[CH2:8][C:5]([NH:4][CH2:2][CH3:3])([C:9]([NH2:11])=[O:10])[CH2:6]3)[N:27]2[N:28]=1

Participants

6

Reactant 4

HCID 10422AzetidineHCID 81531Diisopropylethylamine2×HCID 21083717HCID 21083717, compoundHCID 692108943-(ethylamino)-3-Azetidinecarboxamide hydrochloride

Product 1

HCID 588013161-[2-(2-Chlorophenyl)-3-iodopyrazolo[1,5-a]pyrimidin-7-yl]-3-ethylaminoazetidine-3-carboxylic Acid Amide

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
50 °C

Procedure

To a slurry of 3-ethylaminoazetidine-3-carboxylic acid amide, hydrochloride salt (I-1A-3e; 1.13 g, 5.2 mmol) and diisopropylethylamine (3.2 ml, 18 mmol) in acetone (60 ml) was added 7-chloro-2-(2-chlorophenyl)-3-iodopyrazolo[1,5-a]pyrimidine (I-1A-1d; 1.36 g, 3.48 mmol). The mixture was heated to 50° C. overnight. Additional azetidine and diisopropylethylamine were added in portions until the reaction was judged complete by LCMS. A pale yellow precipitate formed and was isolated by vacuum filtration. The filtrate was concentrated to 20 ml and then diluted with diethyl ether to precipitate additional material that was collected by vacuum filtration. The combined solids were triturated from ether to afford product I-2A-1a as a pale yellow solid (1.3 g, 76%): +ESI MS (M+1) 497.0; 1H NMR (400 MHz, DMSO-D6) δ 8.27 (d, J=5.4 Hz, 1H), 7.59 (d, J=7.9 Hz, 1H), 7.52–7.44 (m, 3H), 7.35 (br s, 1H), 7.30 (br s, 1H), 5.98 (d, J=5.0 Hz, 1H), 2.40–2.30 (m, 2H), 0.99 (t, J=7.1 Hz, 3H).

Workup

  1. customA pale yellow precipitate formed
  2. customwas isolated by vacuum filtration
  3. concentrationThe filtrate was concentrated to 20 ml
  4. additiondiluted with diethyl ether
  5. customto precipitate additional material that
  6. filtrationwas collected by vacuum filtration
  7. customThe combined solids were triturated from ether
  8. customto afford product

Sources & evidence

ORD record
ord-230ce8f19e034f43b442b399847c7f8c
Source dataset
uspto-grants-2007_02
Patent number
US07176210B2

Reaction notes

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