Triethylamine → HCID 71509800, compound

HRID 1499798Notes

Reaction equation

HRID 1499798 reaction equation
Cl.Cl.[NH2:3][C:4]1[N:9]=[CH:8][N:7]=[C:6]2[N:10]([CH:16]([C:18]3[C:19]([O:31][CH3:32])=[C:20]([CH:27]4[CH2:30][NH:29][CH2:28]4)[C:21]([CH3:26])=[C:22]([CH:25]=3)[C:23]#[N:24])[CH3:17])[N:11]=[C:12]([CH:13]([F:15])[F:14])[C:5]=12.[Si]([O:50][C@@H:51]([CH3:54])[CH:52]=O)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C(Cl)Cl.O1CCCC1>[NH2:3][C:4]1[N:9]=[CH:8][N:7]=[C:6]2[N:10]([CH:16]([C:18]3[C:19]([O:31][CH3:32])=[C:20]([CH:27]4[CH2:30][N:29]([CH2:52][C@@H:51]([OH:50])[CH3:54])[CH2:28]4)[C:21]([CH3:26])=[C:22]([CH:25]=3)[C:23]#[N:24])[CH3:17])[N:11]=[C:12]([CH:13]([F:14])[F:15])[C:5]=12

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 2724141Tetrabutylammonium FluorideHCID 5049666Sodium triacetoxyborohydrideHCID 10828944(2S)-2-{[tert-Butyl(diphenyl)silyl]oxy}propanalHCID 86677719HCID 86677719, compound

Product 1

HCID 71509800HCID 71509800, compoundYield 6.7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a mixture of 5-{1-[4-amino-3-(difluoromethyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]ethyl}-3-azetidin-3-yl-4-methoxy-2-methylbenzonitrile dihydrochloride (25 mg, 0.051 mmol), (2S)-2-{[tert-butyl(diphenyl)silyl]oxy}propanal (18 mg, 0.057 mmol) and triethylamine (22 μL, 0.15 mmol) in methylene chloride (0.3 mL) was added sodium triacetoxyborohydride resin (45 mg, 0.10 mmol). The mixture was stirred overnight then filtered and concentrated. To the residue was added tetrahydrofuran (1.0 mL) and 1.0 M tetra-n-butylammonium fluoride in THF (0.51 mL, 0.51 mmol). The resulting mixture was stirred overnight at room temp. The solvent was evaporated and the crude material was purified using 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 1.6 mg (6.6%) of the desired product. The product was isolated as a single diastereomer. LCMS calculated for C23H28F2N7O2 (M+H)+: m/z=472.2; Found: 472.2.

Workup

  1. filtrationthen filtered
  2. concentrationconcentrated
  3. stirringThe resulting mixture was stirred overnight at room temp
  4. customThe solvent was evaporated
  5. customthe crude material was purified
  6. washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min)

Sources & evidence

ORD record
ord-aa5ce9ab64b34b57a7dcc62d90cb182d
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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