Pyridine → HCID 86726654, compound

HRID 1499399Notes

Reaction equation

HRID 1499399 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[S:10][CH:11]=[C:12]([C:14]([OH:16])=O)[N:13]=1.ClC(N(C)C)=C(C)C.[NH2:25][C:26]1[CH:27]=[N:28][C:29]2[C:34]([C:35]=1[N:36]1[CH2:41][CH2:40][CH2:39][C@H:38]([NH:42][C:43](=[O:49])[O:44][C:45]([CH3:48])([CH3:47])[CH3:46])[CH2:37]1)=[CH:33][CH:32]=[CH:31][CH:30]=2.N1C=CC=CC=1>C(Cl)Cl>[F:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=1[C:9]1[S:10][CH:11]=[C:12]([C:14]([NH:25][C:26]2[CH:27]=[N:28][C:29]3[C:34]([C:35]=2[N:36]2[CH2:41][CH2:40][CH2:39][C@H:38]([NH:42][C:43](=[O:49])[O:44][C:45]([CH3:47])([CH3:46])[CH3:48])[CH2:37]2)=[CH:33][CH:32]=[CH:31][CH:30]=3)=[O:16])[N:13]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 242784542-(2,6-Difluorophenyl)-1,3-thiazole-4-carboxylic acidHCID 86726649HCID 86726649, compound

Product 1

HCID 86726654HCID 86726654, compoundYield 94%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a suspension of 2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxylic acid (28.5 mg, 0.118 mmol) in DCM (0.5 mL), a solution of 1-chloro-N,N,2-trimethylpropenylamine (45.0 mg, 0.337 mmol) in DCM (1.0 mL) was added slowly. The mixture was stirred at room temperature for 2 h. A solution of tert-butyl [(3S)-1-(3-aminoquinolin-4-yl)piperidin-3-yl]carbamate (from step 2 in Example 1, 36.9 mg, 0.108 mmol) in DCM (2.0 mL) was added, followed by pyridine (93.2 mg, 1.18 mmol). The mixture was then stirred at room temperature for a further 2 h, and then concentrated under reduced pressure. The resulting residue was purified by chromatography on silica gel (0-100% EtOAc in hexanes) to give the title compound as a pale yellow oil (57.4 mg, 94%). LCMS calc. for C29H30F2N5O3S (M+H)+: m/z=566.2. found 566.2.

Workup

  1. stirringThe mixture was then stirred at room temperature for a further 2 h
  2. concentrationconcentrated under reduced pressure
  3. customThe resulting residue was purified by chromatography on silica gel (0-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-0add94975297432e8220bc3e12d3f974
Source dataset
uspto-grants-2015_12
Patent number
US09200004B2

Reaction notes

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