Diisopropylethylamine → HCID 70498096, compound

HRID 1466661Notes

Reaction equation

HRID 1466661 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:30][CH3:31])=[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]([CH:25]([CH3:29])[C:26](O)=[O:27])[N:9]=2)[CH:7]=1.Cl.[O:33]1[CH2:36][CH:35]([NH2:37])[CH2:34]1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:30][CH3:31])=[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]([CH:25]([CH3:29])[C:26]([NH:37][CH:35]3[CH2:36][O:33][CH2:34]3)=[O:27])[N:9]=2)[CH:7]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 23062080Oxetan-3-amine hydrochlorideHCID 70496855HCID 70496855, compound

Product 1

HCID 70498096HCID 70498096, compoundYield 52.3%

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)propanoic acid (66.0 mg, 0.150 mmol, 1 equiv), oxetan-3-amine hydrochloride (41.0 mg, 0.374 mmol, 2.50 equiv), N,N,N′,N′-tetramethyl-O-(7-azabenzotriazole-1-yl)uranium hexafluorophosphate (114 mg, 0.299 mmol, 2.00 equiv), and N,N-diisopropylethylamine (522 μL, 2.99 mmol, 20.0 equiv) in N,N-dimethylformamide (1.0 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 (10 mL) and ethyl acetate (10 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 (39 mg, 51% yield). 1H NMR (400 MHz, DMSO-d6), δ: 9.70 (s, 1H), 9.33 (m, 1H), 9.02 (d, J=6.5 Hz, 1H), 8.77 (dd, J=4.2, 1.5 Hz, 1H), 8.65 (s, 1H), 8.36 (s, 1H), 7.50 (dd, J=8.9, 2.7 Hz, 1H), 7.38 (d, J=2.6 Hz, 1H), 7.27-7.31 (m, 2H), 5.06 (q, J=7.1 Hz, 1H), 4.80 (m, 1H), 4.73 (m, 2H), 4.44 (m, 2H), 3.84 (s, 3H), 1.66 (d, J=7.1 Hz, 3H). LCMS (ESI): M+H=496.1.

Workup

  1. concentrationthe reaction mixture was concentrated
  2. customthe resulting residue was partitioned between saturated aqueous sodium bicarbonate (10 mL) and ethyl acetate (10 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-d903ea4b9d504ea69e76a26295f9c0d7
Source dataset
uspto-grants-2015_04
Patent number
US08999998B2

Reaction notes

Loading…