1,2-Dichloroethane → HCID 68008144, compound

HRID 526953Notes

Reaction equation

HRID 526953 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15]([NH:17][C@H:18]4[CH2:23][CH2:22][CH2:21][C@@H:20]([NH2:24])[CH2:19]4)[C:14]([F:25])=[CH:13][N:12]=3)=[CH:9][N:8](S(C3C=CC(C)=CC=3)(=O)=O)[C:5]2=[N:6][CH:7]=1.C(OC([N:43]1[CH2:48][CH2:47][O:46][CH:45]([C:49](O)=[O:50])[CH2:44]1)=O)(C)(C)C.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[OH-].[Li+]>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15]([NH:17][C@H:18]4[CH2:23][CH2:22][CH2:21][C@@H:20]([NH:24][C:49]([CH:45]5[O:46][CH2:47][CH2:48][NH:43][CH2:44]5)=[O:50])[CH2:19]4)[C:14]([F:25])=[CH:13][N:12]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1

Participants

8

Reactant 6

HCID 111,2-DichloroethaneHCID 3939Lithium HydroxideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27559654-((Tert-butoxy)carbonyl)morpholine-2-carboxylic acidHCID 68008346(1S,3R)-N1-[2-[5-chloro-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridin-3-yl]-5-fluoro-pyrimidin-4-yl]cyclohexane-1,3-diamine

Product 1

HCID 68008144HCID 68008144, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (1S,3R)—N1-[2-[5-chloro-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridin-3-yl]-5-fluoro-pyrimidin-4-yl]cyclohexane-1,3-diamine (0.06 g, 0.12 mmol) in CH2Cl2 (3 mL) was added 4-tert-butoxycarbonylmorpholine-2-carboxylic acid (40.4 mg, 0.17 mmol), EDC (0.03 g, 0.14 mmol), HOBt (0.02 g, 0.12 mmol) and iPr2NEt (0.06 g, 0.47 mmol), and the reaction mixture was stirred at room temperature overnight. The solvent was evaporated under reduced pressure, and the residue was dissolved in CH2Cl2 (2 mL) and TFA (2 mL) and allowed to stir at room temperature for 2 hours. The resulting solution was concentrated in vacuo, dissolved in THF (4 mL) and treated with 1N aqueous lithium hydroxide (3.0 mL, 3.0 mmol). The reaction mixture was heated in the microwave to 130° C. for 20 min. The solvent was evaporated under reduced pressure, and the residue was purified by HPLC, using 5-70% MeOH/H2O with 6 mM HCl over 15 minutes. The purified fractions were concentrated to provide the bis-hydrochloride of N-[(1R,3S)-3-[[2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoro-pyrimidin-4-yl]amino]cyclohexyl]morpholine-2-carboxamide.

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. dissolutionthe residue was dissolved in CH2Cl2 (2 mL)
  3. stirringto stir at room temperature for 2 hours
  4. concentrationThe resulting solution was concentrated in vacuo
  5. dissolutiondissolved in THF (4 mL)
  6. temperatureThe reaction mixture was heated in the microwave to 130° C. for 20 min
  7. customThe solvent was evaporated under reduced pressure
  8. customthe residue was purified by HPLC
  9. customover 15 minutes
  10. concentrationThe purified fractions were concentrated

Sources & evidence

ORD record
ord-2a6d7da189a94b7783e5f43db0664cd1
Source dataset
uspto-grants-2016_05
Patent number
US09345708B2

Reaction notes

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