Pyridine → HCID 86726660, compound

HRID 1499406Notes

Reaction equation

HRID 1499406 reaction equation
ClC(N(C)C)=C(C)C.[F:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[C:11]=1[C:17]1[S:18][CH:19]=[C:20]([C:22]([OH:24])=O)[N:21]=1.[NH2:25][C:26]1[C:27]([N:35]2[CH2:40][CH2:39][CH2:38][C@H:37]([NH:41][C:42](=[O:48])[O:43][C:44]([CH3:47])([CH3:46])[CH3:45])[CH2:36]2)=[C:28]2[CH:34]=[CH:33][S:32][C:29]2=[N:30][CH:31]=1.N1C=CC=CC=1>C(Cl)Cl>[F:16][C:12]1[CH:13]=[CH:14][CH:15]=[C:10]([F:9])[C:11]=1[C:17]1[S:18][CH:19]=[C:20]([C:22]([NH:25][C:26]2[C:27]([N:35]3[CH2:40][CH2:39][CH2:38][C@H:37]([NH:41][C:42](=[O:48])[O:43][C:44]([CH3:46])([CH3:45])[CH3:47])[CH2:36]3)=[C:28]3[CH:34]=[CH:33][S:32][C:29]3=[N:30][CH:31]=2)=[O:24])[N:21]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 242784542-(2,6-Difluorophenyl)-1,3-thiazole-4-carboxylic acidHCID 86726657HCID 86726657, compound

Product 1

HCID 86726660HCID 86726660, compoundYield 98.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A solution of 1-chloro-N,N,2-trimethylpropenylamine (88.5 mg, 0.662 mmol) in DCM (1.0 mL) was added slowly to a suspension of 2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxylic acid (from step 2 in Example 2, 56.9 mg, 0.236 mmol) in DCM (0.5 mL). The mixture was stirred at room temperature for 2 h. A solution of tert-butyl [(3S)-1-(5-aminothieno[2,3-b]pyridin-4-yl)piperidin-3-yl]carbamate (73.3 mg, 0.210 mmol) in DCM (2.0 mL), followed by pyridine (162.6 mg, 2.056 mmol) was then added and the mixture was stirred at room temperature for a further 2 h. The reaction mixture was then concentrated under reduced pressure and the resulting residue was purified by chromatography on silica gel (0-100% EtOAc in hexanes) to give the sub-title compound as a dark oil (118.2 mg, 98%). LCMS calc. for C27H28F2N5O3S2 (M+H)+: m/z=572.2. found 572.2.

Workup

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

Sources & evidence

ORD record
ord-8162bd66af484c7c89b9179eadf49b45
Source dataset
uspto-grants-2015_12
Patent number
US09200004B2

Reaction notes

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