Formaldehyde → HCID 86677678, compound

HRID 1499749Notes

Reaction equation

HRID 1499749 reaction equation
Cl.Cl.[NH:3]1[CH2:6][CH:5]([C:7]2[C:8]([O:28][CH3:29])=[C:9]([CH:15]([N:17]3[C:21]4=[N:22][CH:23]=[N:24][C:25]([NH2:26])=[C:20]4[C:19]([CH3:27])=[N:18]3)[CH3:16])[CH:10]=[C:11]([Cl:14])[C:12]=2[F:13])[CH2:4]1.C(N([CH2:35][CH3:36])CC)C.C=O.[C:39](O[BH-](OC(=O)C)OC(=O)C)(=[O:41])C.[Na+]>CO.O1CCCC1.C(#N)C>[Cl:14][C:11]1[C:12]([F:13])=[C:7]([CH:5]2[CH2:4][N:3]([CH:36]3[CH2:35][O:41][CH2:39]3)[CH2:6]2)[C:8]([O:28][CH3:29])=[C:9]([CH:15]([N:17]2[C:21]3=[N:22][CH:23]=[N:24][C:25]([NH2:26])=[C:20]3[C:19]([CH3:27])=[N:18]2)[CH3:16])[CH:10]=1

Participants

8

Reactant 4

HCID 712FormaldehydeHCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 86677675HCID 86677675, compound

Product 1

HCID 86677678HCID 86677678, compoundYield 6.5%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 1-[1-(3-azetidin-3-yl-5-chloro-4-fluoro-2-methoxyphenyl)ethyl]-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine dihydrochloride (19 mg, 0.041 mmol racemic intermediate from Example 67, Step 1) and triethylamine (28 μL, 0.20 mmol) in methanol (0.1 mL)/acetonitrile (0.1 mL)/tetrahydrofuran (0.1 mL) was added 37% formaldehyde (15 μL, 0.20 mmol), followed by sodium triacetoxyborohydride (22 mg, 0.10 mmol). The resulting mixture was stirred overnight at room temperature. The mixture was purified on RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min) to give the desired product (1.2 mg, 6.3%). The product was isolated as a racemic mixture. LCMS calculated for C19H23ClFN6O (M+H)+: m/z=405.2; Found: 405.1.

Workup

  1. customThe mixture was purified on RP-HPLC (XBridge C18 column
  2. washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min)

Sources & evidence

ORD record
ord-d056621903aa4fcbad0ce5886d65f8d1
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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