4-Fluorophenylboronic acid → HCID 58387576, compound

HRID 1028056Notes

Reaction equation

HRID 1028056 reaction equation
[NH2:1][C:2]1[C:3]([C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][N:18]=2)[N:15]=[CH:14][CH:13]=[C:12]3[N:19]2[CH2:24][CH2:23][CH2:22][C@H:21]([NH:25]C(=O)OC(C)(C)C)[CH2:20]2)=[N:4][C:5](Cl)=[CH:6][CH:7]=1.[F:33][C:34]1[CH:39]=[CH:38][C:37](B(O)O)=[CH:36][CH:35]=1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.COCCOC>[NH2:25][C@H:21]1[CH2:22][CH2:23][CH2:24][N:19]([C:12]2[C:11]3[C:16](=[CH:17][N:18]=[C:9]([C:3]4[C:2]([NH2:1])=[CH:7][CH:6]=[C:5]([C:37]5[CH:38]=[CH:39][C:34]([F:33])=[CH:35][CH:36]=5)[N:4]=4)[CH:10]=3)[N:15]=[CH:14][CH:13]=2)[CH2:20]1

Participants

5

Reactant 2

HCID 2856454-Fluorophenylboronic acidHCID 86656453HCID 86656453, compound

Product 1

HCID 58387576HCID 58387576, compoundYield 61%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

A solution of (S)-tert-butyl 1-(6-(3-amino-6-chloropyridin-2-yl)-1,7-naphthyridin-4-yl)piperidin-3-ylcarbamate (1.0 equiv.), 4-fluorophenylboronic acid (3.0 equiv.) and Pd(dppf)Cl2—CH2Cl2 (0.15 equiv.) in 3:1 DME/2M Na2CO3 was heated in a microwave at 120° C. for 20 minutes. Upon cooling, the solution was partitioned between EtOAc and Na2CO3(sat.) washed further with NaCl(sat.), dried over MgSO4, concentrated and purified by RP HPLC. Upon lyophilization, the Boc group was deprotected by treatment with 25% TFA/CH2Cl2, concentrated, purified by RP-HPLC and lyophilized to yield (S)-2-(4-(3-aminopiperidin-1-yl)-1,7-naphthyridin-6-yl)-6-(4-fluorophenyl)pyridin-3-amine (61%). LC/MS=415.2 (M+H), LC=2.32 min.

Workup

  1. temperatureUpon cooling
  2. customthe solution was partitioned between EtOAc and Na2CO3(sat.)
  3. washwashed further with NaCl(sat.)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. custompurified by RP HPLC
  7. concentrationconcentrated
  8. custompurified by RP-HPLC

Sources & evidence

ORD record
ord-8d7d71077d0f4c63a381b68ef13edeb9
Source dataset
uspto-grants-2014_05
Patent number
US08735424B2

Reaction notes

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