Water → HCID 86677790, compound

HRID 1499866Notes

Reaction equation

HRID 1499866 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([C:14]3[CH:21]=[C:20]([Cl:22])[C:17]([C:18]#[N:19])=[C:16]([CH:23]4[CH2:26][NH:25][CH2:24]4)[C:15]=3[O:27][CH2:28][CH3:29])[CH3:13])[N:9]=[C:10]([CH3:11])[C:3]=12.C(=O)([O-])[O-].[K+].[K+].Br[C:37]([CH3:46])([CH3:45])[C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39].O>CN(C)C=O>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([C:14]3[C:15]([O:27][CH2:28][CH3:29])=[C:16]([CH:23]4[CH2:24][N:25]([C:37]([CH3:46])([CH3:45])[C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:26]4)[C:17]([C:18]#[N:19])=[C:20]([Cl:22])[CH:21]=3)[CH3:13])[N:9]=[C:10]([CH3:11])[C:3]=12

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 90290tert-Butyl 2-bromo-2-methylpropionateHCID 86677785HCID 86677785, compound2×

Product 1

HCID 86677790HCID 86677790, compoundYield 84.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 4-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-2-azetidin-3-yl-6-chloro-3-ethoxybenzonitrile (0.38 g, 0.92 mmol, chiral intermediate from Example 212) in N,N-dimethylformamide (4.6 mL) was treated with potassium carbonate (0.51 g, 3.7 mmol) followed by tert-butyl 2-bromo-2-methylpropanoate (0.86 mL, 4.6 mmol) and heated at 60° C. for 3 h. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was separated, dried with magnesium sulfate, filtered, and concentrated to a crude oil. The crude material was purified by flash column chromatography using methanol in dichloromethane (0%-10%) to give the desired product (0.43 g, 83%). The product was isolated as a single enantiomer. 1H NMR (300 MHz, DMSO-d6) δ 8.10 (s, 1H), 7.44 (s, 1H), 6.22 (q, J=6.8 Hz, 1H), 4.12-3.97 (m, 1H), 3.88-3.70 (m, 4H), 3.62-3.48 (m, 2H), 2.54 (s, 3H), 1.70 (d, J=7.0 Hz, 3H), 1.33 (t, J=6.9 Hz, 3H), 1.17 (s, 9H), 1.05 (s, 6H). LCMS for C28H37ClN7O3 (M+H)+: m/z=554.3; Found: 554.3.

Workup

  1. extractionextracted with ethyl acetate
  2. customThe organic layer was separated
  3. dry with materialdried with magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated to a crude oil
  6. customThe crude material was purified by flash column chromatography

Sources & evidence

ORD record
ord-fb077cd47b2742e6a0b5366f9c79294d
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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