Pyridine → HCID 86726658, compound

HRID 1499404Notes

Reaction equation

HRID 1499404 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[S:13][C:12]([C:14]2[C:19]([F:20])=[CH:18][CH:17]=[CH:16][C:15]=2[F:21])=[N:11][C:10]=1[C:22](O)=[O:23])=[O:7])([CH3:4])([CH3:3])[CH3:2].ClC(N(C)C)=C(C)C.[NH2:33][C:34]1[C:35]([N:43]2[CH2:48][CH2:47][CH2:46][C@H:45]([NH:49][C:50](=[O:56])[O:51][C:52]([CH3:55])([CH3:54])[CH3:53])[CH2:44]2)=[C:36]2[CH:42]=[CH:41][S:40][C:37]2=[N:38][CH:39]=1.N1C=CC=CC=1>C1COCC1>[C:1]([O:5][C:6]([NH:8][C:9]1[S:13][C:12]([C:14]2[C:19]([F:20])=[CH:18][CH:17]=[CH:16][C:15]=2[F:21])=[N:11][C:10]=1[C:22]([NH:33][C:34]1[C:35]([N:43]2[CH2:48][CH2:47][CH2:46][C@H:45]([NH:49][C:50](=[O:56])[O:51][C:52]([CH3:53])([CH3:55])[CH3:54])[CH2:44]2)=[C:36]2[CH:42]=[CH:41][S:40][C:37]2=[N:38][CH:39]=1)=[O:23])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 1049PyridineHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 674381985-((Tert-butoxycarbonyl)amino)-2-(2,6-difluorophenyl)thiazole-4-carboxylic acidHCID 86726657HCID 86726657, compound

Product 1

HCID 86726658HCID 86726658, compoundYield 84%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of 5-[(tert-butoxycarbonyl)amino]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxylic acid (Example 1, step 6, 176.4 mg, 0.4950 mmol) in THF (0.5 mL), a solution of 1-chloro-N,N,2-trimethylpropenylamine (169.8 mg, 1.271 mmol) in THF (1.0 mL) was added slowly. The mixture was stirred at room temperature for 5 h. A solution of tert-butyl [(3S)-1-(5-aminothieno[2,3-b]pyridin-4-yl)piperidin-3-yl]carbamate (139.6 mg, 0.4006 mmol) in THF (2.0 mL) was then added to the resulting mixture, followed by pyridine (316.1 mg, 3.996 mmol), and the mixture was stirred at room temperature for a further 2 h. The mixture was then concentrated under reduced pressure and the resulting residue was purified by chromatography on silica gel (0-100% EtOAc in hexanes) to afford the sub-title compound as a dark semi-solid (230.7 mg, 84%). LCMS calc. for C32H37F2N6O5S2 (M+H)+: m/z=687.2. found 687.2.

Workup

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

Sources & evidence

ORD record
ord-69901fb4ad8f46328b1d8b1503870bb8
Source dataset
uspto-grants-2015_12
Patent number
US09200004B2

Reaction notes

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