Hydrochloric Acid → HCID 86677687, compound

HRID 1499756Notes

Reaction equation

HRID 1499756 reaction equation
Cl.Cl.[NH:3]1[CH2:6][CH:5]([C:7]2[C:8]([O:30][CH3:31])=[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]([CH:27]([F:29])[F:28])=[N:18]3)[CH3:16])[CH:10]=[C:11]([Cl:14])[C:12]=2[F:13])[CH2:4]1.[Si]([O:39][CH2:40][CH:41]=O)(C(C)(C)C)(C)C.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].Cl.O>C(Cl)Cl>[NH2:26][C:25]1[N:24]=[CH:23][N:22]=[C:21]2[N:17]([CH:15]([C:9]3[C:8]([O:30][CH3:31])=[C:7]([CH:5]4[CH2:6][N:3]([CH2:41][CH2:40][OH:39])[CH2:4]4)[C:12]([F:13])=[C:11]([Cl:14])[CH:10]=3)[CH3:16])[N:18]=[C:19]([CH:27]([F:29])[F:28])[C:20]=12

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 962WaterHCID 8471TriethylamineHCID 41877882-((Tert-butyldimethylsilyl)oxy)acetaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 86677683HCID 86677683, compound

Product 1

HCID 86677687HCID 86677687, compoundYield 5.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 1-[1-(3-azetidin-3-yl-5-chloro-4-fluoro-2-methoxyphenyl)ethyl]-3-(difluoromethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine dihydrochloride (45 mg, 0.090 mmol), {[tert-butyl(dimethyl)silyl]oxy}acetaldehyde (110 mg, 0.63 mmol) and triethylamine (63 μL, 0.45 mmol) in methylene chloride (0.9 mL) was added sodium triacetoxyborohydride resin (0.12 g, 0.27 mmol). The mixture was stirred at room temperature for 2 h, then filtered. The filtrate was treated with 6.0 M hydrogen chloride in water (0.2 mL, 0.9 mmol), and 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, 5.6%). LCMS calculated for C20H23ClF3N6O2 (M+H)+: m/z=471.1; Found: 471.2. The racemic product was separated on a Phenomenex Lux Cellulose-4 column, eluting with 20% ethanol in hexanes, at flow rate of 18 mL/min, and column loading of ˜4 mg/injection to separate two enantiomers. First peak retention time 13.1 min; second peak retention time 16.3 min.

Workup

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

Sources & evidence

ORD record
ord-4aabd33d03c243859d020361fb996723
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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