1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 6-Pyrazol-1-yl-imidazo[1,2-a]pyridine-2-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide

HRID 1093876Notes

Reaction equation

HRID 1093876 reaction equation
CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[N:31]1([C:36]2[CH:37]=[CH:38][C:39]3[N:40]([CH:42]=[C:43]([C:45]([OH:47])=O)[N:44]=3)[CH:41]=2)[CH:35]=[CH:34][CH:33]=[N:32]1.Cl.[NH2:49][CH2:50][C:51]([N:53]1[CH2:58][CH2:57][CH:56]([O:59][C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][C:61]=2[Cl:66])[CH2:55][CH2:54]1)=[O:52]>CN(C=O)C.O>[Cl:66][C:61]1[CH:62]=[CH:63][CH:64]=[CH:65][C:60]=1[O:59][CH:56]1[CH2:55][CH2:54][N:53]([C:51](=[O:52])[CH2:50][NH:49][C:45]([C:43]2[N:44]=[C:39]3[CH:38]=[CH:37][C:36]([N:31]4[CH:35]=[CH:34][CH:33]=[N:32]4)=[CH:41][N:40]3[CH:42]=2)=[O:47])[CH2:58][CH2:57]1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 578744966-Pyrazol-1-yl-imidazo[1,2-a]pyridine-2-carboxylic acidHCID 665915282-Amino-1-[4-(2-chloro-phenoxy)-piperidin-1-yl]-ethanone hydrochloride

Product 1

HCID 578745136-Pyrazol-1-yl-imidazo[1,2-a]pyridine-2-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amideYield 36.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (169 mg, 1.3 mmol) followed by HOBt (39 mg, 0.29 mmol) and EDCI (75 mg, 0.39 mmol) was added to a stirred solution of 6-pyrazol-1-yl-imidazo[1,2-a]pyridine-2-carboxylic acid (60 mg, 0.26 mmol) in DMF (1 mL). After 2 minutes of stirring, 2-amino-1-[4-(2-chloro-phenoxy)-piperidin-1-yl]-ethanone hydrochloride (80 mg, 0.26 mmol) (prepared according to Step 1 and 5 of the General Scheme) was added and the resulting mixture was stirred at room temperature overnight. Cold water was added and the reaction mixture was partitioned with ethyl acetate, the organic layer was dried over sodium sulfate and concentrated under reduced pressure. Purification by preparative HPLC afforded 45 mg (33% Yield) of 6-pyrazol-1-yl-imidazo[1,2-a]pyridine-2-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 479, 97.25%. 1H NMR (300 MHz, DMSO-d6): δ 9.2 (s, 1H), 8.5 (m, 2H), 8.4 (t, 1H), 8.0 (dd, 1H), 7.8 (m, 2H), 7.4 (dd, 1H), 7.53 (m, 2H), 7.0 (m, 1H), 6.6 (t, 1H), 4.8 (m, 1H), 4.0 (bs, 1H), 4.2 (d, 2H), 3.7 (m, 2H), 3.4 (m, 2H), 2.0 (m, 2H), 1.7 (m, 2H).

Workup

  1. additionwas added
  2. stirringthe resulting mixture was stirred at room temperature overnight
  3. customthe reaction mixture was partitioned with ethyl acetate
  4. dry with materialthe organic layer was dried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-bdb4d2435036427f96034b2b823f66e9
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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