Acetic Acid → HCID 86677814, compound

HRID 1499891Notes

Reaction equation

HRID 1499891 reaction equation
[NH:1]1[CH2:4][CH:3]([C:5]2[C:6]([O:26][CH3:27])=[C:7]([CH:13]([N:15]3[C:19]4=[N:20][CH:21]=[N:22][C:23]([NH2:24])=[C:18]4[C:17]([CH3:25])=[N:16]3)[CH3:14])[CH:8]=[C:9]([Cl:12])[C:10]=2[Cl:11])[CH2:2]1.C([BH3-])#N.[Na+].[CH:32](=O)[CH3:33].C(O)(=O)C>CO>[Cl:11][C:10]1[C:9]([Cl:12])=[CH:8][C:7]([CH:13]([N:15]2[C:19]3=[N:20][CH:21]=[N:22][C:23]([NH2:24])=[C:18]3[C:17]([CH3:25])=[N:16]2)[CH3:14])=[C:6]([O:26][CH3:27])[C:5]=1[CH:3]1[CH2:2][N:1]([CH2:32][CH3:33])[CH2:4]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 177AcetaldehydeHCID 5003444Sodium cyanoborohydrideHCID 86677815HCID 86677815, compound

Product 1

HCID 86677814HCID 86677814, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
20 °C

Procedure

A solution of 1-[1-(3-azetidin-3-yl-4,5-dichloro-2-methoxyphenyl)ethyl]-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (40 mg, 0.098 mmol) in methanol (2.6 mL) was treated with sodium cyanoborohydride (15 mg, 0.25 mmol) followed by acetaldehyde (22 μL, 0.39 mmol) and stirred at 20° C. for 20 min. The reaction mixture was quenched with acetic acid (130 μL, 2.3 mmol), diluted with methanol, and purified by preparative LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min) to give the desired product as a mixture of enantiomers. This racemic mixture was separated by chiral HPLC (RT=18.6 min and 22.0 min; Phenomenex Lux Cellulose C-4 column, 21.2×250 mm, 5 micron particle size, eluting with 5% ethanol in hexanes at 18 ml/min, 2.5 mg/inj) to give the desired peak 1 isomer (11 mg, 26%). 1H NMR (300 MHz, DMSO-d6) δ 8.11 (s, 1H), 7.45 (s, 1H), 7.33 (br s, 2H), 6.21 (q, J=6.9 Hz, 1H), 3.98-3.77 (m, 3H), 3.57 (s, 3H), 2.92-2.83 (m, 1H), 2.79-2.72 (m, 1H), 2.55 (s, 3H), 2.35-2.22 (m, 2H), 1.70 (d, J=7.1 Hz, 3H), 0.86 (t, J=7.1 Hz, 3H). LCMS for C20H25Cl2N6O (M+H)+: m/z=435.1; Found: 435.0.

Workup

  1. custompurified by preparative LCMS (XBridge C18 column
  2. washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min)

Sources & evidence

ORD record
ord-7ff21d360f214f339fa777f72fe030a7
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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