HCID 58387588, compound → HCID 58387593, compound

HRID 1028054Notes

Reaction equation

HRID 1028054 reaction equation
CC1(C)C(C)(C)OB([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)O1.[NH2:34][C:35]1[CH:36]=[CH:37][C:38]([C:42]2[CH:43]=[C:44]([CH:51]=[CH:52][C:53]=2[F:54])[C:45]([NH:47][CH:48]([CH3:50])[CH3:49])=[O:46])=[N:39][C:40]=1Cl>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>[NH2:34][C:35]1[CH:36]=[CH:37][C:38]([C:42]2[CH:43]=[C:44]([CH:51]=[CH:52][C:53]=2[F:54])[C:45]([NH:47][CH:48]([CH3:50])[CH3:49])=[O:46])=[N:39][C:40]=1[C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][N:18]=1)[N:15]=[CH:14][CH:13]=[C:12]2[N:19]1[CH2:24][CH2:23][CH2:22][C@H:21]([NH2:25])[CH2:20]1

Participants

5

Reactant 2

HCID 58387588HCID 58387588, compoundHCID 67315265HCID 67315265, compound

Product 1

HCID 58387593HCID 58387593, compoundYield 21%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

A solution of (S)-tert-butyl 1-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,7-naphthyridin-4-yl)piperidin-3-ylcarbamate (1.0 equiv.), 3-(5-amino-6-chloropyridin-2-yl)-4-fluoro-N-isopropylbenzamide ((1.0 equiv.) and Pd(dppf)Cl2—CH2Cl2 (0.2 equiv.) in 3:1 DME/2M Na2CO3 was heated at 120° C. for 20 hours. 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)-3-(5-amino-6-(4-(3-aminopiperidin-1-yl)-1,7-naphthyridin-6-yl)pyridin-2-yl)-4-fluoro-N-isopropylbenzamide (21%). LC/MS=500.3 (M+H), LC=2.36 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-43e6dde44adb4060ba7d656151c0f97b
Source dataset
uspto-grants-2014_05
Patent number
US08735424B2

Reaction notes

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