tert-Butyl piperazine-1-carboxylate → HCID 90014003, compound

HRID 2279169Notes

Reaction equation

HRID 2279169 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[N:20]=[C:19]3[N:21]([CH:25]4[CH2:30][CH2:29][CH2:28][CH2:27][O:26]4)[N:22]=[C:23]([CH3:24])[C:18]3=[C:17]([C:31](=O)[CH3:32])[CH:16]=2)=[C:11]([F:34])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:35]([O:39][C:40]([N:42]1[CH2:47][CH2:46][NH:45][CH2:44][CH2:43]1)=[O:41])([CH3:38])([CH3:37])[CH3:36].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C>ClCCl.C(O)(=O)C>[C:35]([O:39][C:40]([N:42]1[CH2:47][CH2:46][N:45]([CH:31]([C:17]2[CH:16]=[C:15]([C:12]3[CH:13]=[CH:14][C:9]([O:8][CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)=[CH:10][C:11]=3[F:34])[N:20]=[C:19]3[N:21]([CH:25]4[CH2:30][CH2:29][CH2:28][CH2:27][O:26]4)[N:22]=[C:23]([CH3:24])[C:18]=23)[CH3:32])[CH2:44][CH2:43]1)=[O:41])([CH3:38])([CH3:36])[CH3:37]

Participants

7

Reactant 4

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 2724942TriacetoxyborohydrideHCID 5049666Sodium triacetoxyborohydrideHCID 90013858HCID 90013858, compound

Product 1

HCID 90014003HCID 90014003, compoundYield 16.8%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of 1-[6-(4-benzyloxy-2-fluoro-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl]-ethanone (390 mg), acetic acid (25 μL), piperazine-1-carboxylic acid tert-butyl ester (158 mg) and sodium triacetoxy borohydride (270 mg) in dichloromethane (7.5 mL) was stirred at 40° C. overnight. Then additional triacetoxy borohydride (90 mg) was added. The reaction mixture was concentrated in a membrane pump vacuum, and the residue was purified by flash chromatography (silica, heptane/ethyl acetate gradient) giving 4-{1-[6-(4-Benzyloxy-2-fluoro-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl]-ethyl}-piperazine-1-carboxylic acid tert-butyl ester (90 mg). This material was dissolved in methanol (5 mL), purged with argon, then with hydrogen and palladium (10% on charcoal, 8 mg) was added. The reaction mixture was stirred at 40° C. until the reaction was complete (according to HPLC/MS). The catalyst was filtered off and the filtrate was concentrated in a membrane pump vacuum. The residue was taken up in THF (2 mL), and conc. hydrochloric acid (1 mL) was added. The solution was stirred at r.t., then the solvents were evaporated and the residue was purified by preparative HPLC (C18 column, acetonitrile/water gradient) giving 3-fluoro-4-[3-methyl-4-(1-piperazin-1-yl-ethyl)-1H-pyrazolo[3,4-b]pyridin-6-yl]-phenol (30 mg, 9%).

Workup

  1. concentrationThe reaction mixture was concentrated in a membrane pump vacuum
  2. customthe residue was purified by flash chromatography (silica, heptane/ethyl acetate gradient)

Sources & evidence

ORD record
ord-7330cb3f3715412a94348ce6819a6580
Source dataset
uspto-grants-2015_09
Patent number
US09133181B2

Reaction notes

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