Hydrochloric Acid → HCID 86677677, compound

HRID 1499748Notes

Reaction equation

HRID 1499748 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(CC)CC)C.[Si]([O:44][CH2:45][CH:46]=O)(C(C)(C)C)(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].Cl.O>CO.O1CCCC1.C(#N)C>[NH2:26][C:25]1[N:24]=[CH:23][N:22]=[C:21]2[N:17]([CH:15]([C:9]3[C:8]([O:28][CH3:29])=[C:7]([CH:5]4[CH2:4][N:3]([CH2:46][CH2:45][OH:44])[CH2:6]4)[C:12]([F:13])=[C:11]([Cl:14])[CH:10]=3)[CH3:16])[N:18]=[C:19]([CH3:27])[C:20]=12

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 962WaterHCID 8471TriethylamineHCID 41877882-((Tert-butyldimethylsilyl)oxy)acetaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 86677675HCID 86677675, compound

Product 1

HCID 86677677HCID 86677677, compoundYield 14%

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 {[tert-butyl(dimethyl)silyl]oxy}acetaldehyde (39 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 treated with 6.0 M hydrogen chloride in water (0.07 mL, 0.4 mmol) at room temperature for 10 min and then 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 (2.5 mg, 13%). The product was isolated as a racemic mixture. LCMS calculated for C20H25ClFN6O2 (M+H)+: m/z=435.2; Found: 435.1.

Workup

  1. custompurified 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-f6ae2bf169e5416e8a66c0e0b07b45ef
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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