Formaldehyde → HCID 86677787, compound

HRID 1499863Notes

Reaction equation

HRID 1499863 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.[C:32]([BH3-])#N.[Na+]>CO>[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[CH2:24][N:25]([CH3:32])[CH2:26]4)[C:15]=3[O:27][CH2:28][CH3:29])[CH3:13])[N:9]=[C:10]([CH3:11])[C:3]=12

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 86677785HCID 86677785, compound

Product 1

HCID 86677787HCID 86677787, compoundYield 51.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

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 (chiral intermediate in Example 212, Step 6) (0.30 g, 0.73 mmol) in methanol (7.3 mL) was treated with formaldehyde (37% in water) (0.54 mL, 7.3 mmol) and this was stirred at room temperature for 5 min. The reaction mixture was treated with sodium cyanoborohydride (0.092 g, 1.5 mmol) and stirred at room temperature for 2 h. The reaction mixture was 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 (0.16 g, 50%). The product was isolated as a single enantiomer. 1H NMR (400 MHz, DMSO-d6) δ 8.11 (s, 1H), 7.48 (s, 1H), 6.27-6.18 (m, 1H), 4.10-3.98 (m, 1H), 3.96-3.86 (m, 2H), 3.83-3.74 (m, 1H), 3.72-3.64 (m, 1H), 3.10-2.98 (m, 2H), 2.54 (s, 3H), 2.20 (s, 3H), 1.71 (d, J=6.9 Hz, 3H), 1.32 (t, J=6.7 Hz, 3H). LCMS for C21H25ClN7O (M+H)+: m/z=426.2; Found: 426.2.

Workup

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

Sources & evidence

ORD record
ord-bc06fa77d5f94a8da21124f5760c9eec
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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