Acetic Anhydride → [(3s)-3-[1-(3-Chloropyridin-2-yl)pyrazolo[4,5-e]pyrimidin-4-yl]oxy-4-[(5-methylpyridin-2-yl)amino]-4-oxobutyl]acetate

HRID 1098018Notes

Reaction equation

HRID 1098018 reaction equation
[C:1]([O:4][C:5](=O)[CH3:6])(=[O:3])[CH3:2].[Cl:8][C:9]1[C:10]([N:15]2[C:19]3=[N:20][CH:21]=[N:22][C:23]([O:24][C@@H:25](CCO)[C:26]([NH:28][C:29]4[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][N:30]=4)=[O:27])=[C:18]3[CH:17]=[N:16]2)=[N:11][CH:12]=[CH:13][CH:14]=1.C(N(CC)C(C)C)(C)C>CN(C)C1C=CN=CC=1.C(Cl)Cl>[Cl:8][C:9]1[C:10]([N:15]2[C:19]3[N:20]=[CH:21][N:22]=[C:23]([O:24][C@H:25]([C:26]([NH:28][C:29]4[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][N:30]=4)=[O:27])[CH2:6][CH2:5][O:4][C:1](=[O:3])[CH3:2])[C:18]=3[CH:17]=[N:16]2)=[N:11][CH:12]=[CH:13][CH:14]=1

Participants

6

Reactant 3

HCID 7918Acetic AnhydrideHCID 81531DiisopropylethylamineHCID 57504373(2S)-2-[1-(3-chloro-2-pyridyl)pyrazolo[4,5-e]pyrimidin-4-yl]oxy-4-hydroxy-N-(5-methyl-2-pyridyl)butanamide

Product 1

HCID 59279459[(3s)-3-[1-(3-Chloropyridin-2-yl)pyrazolo[4,5-e]pyrimidin-4-yl]oxy-4-[(5-methylpyridin-2-yl)amino]-4-oxobutyl]acetateYield 45.8%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Acetic anhydride (0.035 mL, 0.38 mmol) was added to (2S)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-4-hydroxy-N-(5-methylpyridin-2-yl)butanamide (Example 143) (150 mg, 0.34 mmol), N,N-Diisopropylethylamine (0.089 mL, 0.51 mmol) and 4-dimethylaminopyridine (4.17 mg, 0.03 mmol) in DCM (2 mL) at 0° C. over a period of 5 minutes under nitrogen. The resulting solution was stirred at 0° C. for 25 minutes. The volatiles were removed under reduced pressure and the crude product was purified by flash silica chromatography, eluting with 0 to 100% ethyl acetate in isohexane to afford the product (75 mg, 45.6%). 1H NMR (400 MHz, CDCl3) δ 1.95 (3H, s), 2.29 (3H, s), 2.54 (2H, q), 4.31-4.39 (2H, m), 6.00 (1H, t), 7.45-7.49 (1H, m), 7.53 (1H, d), 8.00-8.02 (1H, m), 8.10-8.14 (2H, m), 8.43 (1H, s), 8.61 (1H, q), 8.64 (1H, s), 8.80 (1H, s); m/z (ES+) (M+H)+=482; HPLC tR=2.04 min.

Workup

  1. customThe volatiles were removed under reduced pressure
  2. customthe crude product was purified by flash silica chromatography
  3. washeluting with 0 to 100% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-788aa66c45304f85aef51b09e019c94c
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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