Azetidine → HCID 70499062, compound

HRID 1466664Notes

Reaction equation

HRID 1466664 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:31][CH3:32])=[C:6]([C:8]2[C:12]([NH:13][C:14]([C:16]3[C:24]4[N:23]=[CH:22][N:21]=[CH:20][C:19]=4[NH:18][N:17]=3)=[O:15])=[CH:11][N:10]([C:25]([CH3:30])([CH3:29])[C:26](O)=[O:27])[N:9]=2)[CH:7]=1.[NH:33]1[CH2:36][CH2:35][CH2:34]1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[N:33]1([C:26](=[O:27])[C:25]([N:10]2[CH:11]=[C:12]([NH:13][C:14]([C:16]3[C:24]4[N:23]=[CH:22][N:21]=[CH:20][C:19]=4[NH:18][N:17]=3)=[O:15])[C:8]([C:6]3[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=3[O:31][CH3:32])=[N:9]2)([CH3:30])[CH3:29])[CH2:36][CH2:35][CH2:34]1

Participants

5

Reactant 3

HCID 10422AzetidineHCID 81531DiisopropylethylamineHCID 70497839HCID 70497839, compound

Product 1

HCID 70499062HCID 70499062, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 2-(3-(5-chloro-2-methoxyphenyl)-4-(pyrazolo pyrimidine-3-carboxamido)-1H-pyrazol-1-yl)-2-methylpropanoic acid (0.050 g, 0.11 mmol, 1 equiv), azetidine (18.5 μL, 0.275 mmol, 2.50 equiv), N,N,N′,N′-tetramethyl-O-(7-azabenzotriazole-1-yl)uranium hexafluorophosphate (84 mg, 0.20 mmol, 2.00 equiv), and N,N-diisopropylethylamine (380 μL, 2.2 mmol, 20 equiv) in N,N-dimethylformamide (1 mL) was heated at 50° C. After 6 h, the reaction mixture was concentrated, and the resulting residue was partitioned between saturated aqueous sodium bicarbonate (5 mL) and ethyl acetate (5 mL). The aqueous was extracted with ethyl acetate (2×5 mL). The combined organic was dried over anhydrous sodium sulfate, filtered, and concentrated. Purification by preparative HPLC afforded product (32 mg, 60% yield). 1H NMR (400 MHz, DMSO-d6), δ: 9.70 (s, 1H), 9.34 (m, 1H), 8.77 (dd, J=4.2, 1.5 Hz, 1H), 8.64 (s, 1H), 8.36 (s, 1H), 7.52 (dd, J=8.9, 2.7 Hz, 1H), 7.41 (d, J=2.6 Hz, 1H), 7.28-7.32 (m, 2H), 3.88 (s, 2H), 3.86 (s, 3H), 3.41 (m, 2H), 2.04 (m, 2H), 1.72 (s, 6H). LCMS (ESI): M+H=494.1.

Workup

  1. concentrationthe reaction mixture was concentrated
  2. customthe resulting residue was partitioned between saturated aqueous sodium bicarbonate (5 mL) and ethyl acetate (5 mL)
  3. extractionThe aqueous was extracted with ethyl acetate (2×5 mL)
  4. dry with materialThe combined organic was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-9ed9c75d6eaa4572a306dea703125b42
Source dataset
uspto-grants-2015_04
Patent number
US08999998B2

Reaction notes

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