4-Methylmorpholine → HCID 67003306, compound

HRID 2362641Notes

Reaction equation

HRID 2362641 reaction equation
[Cl:1][C:2]1[C:3]([C:20]2[S:24][C:23]([C:25]3([OH:29])[CH2:28][CH2:27][CH2:26]3)=[N:22][CH:21]=2)=[C:4]2[CH:10]=[C:9]([C:11]3[CH:19]=[CH:18][C:14]([C:15]([OH:17])=O)=[CH:13][CH:12]=3)[NH:8][C:5]2=[N:6][CH:7]=1.[CH3:30][N:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1.CN1CCOCC1.OC1C2N=NNC=2C=CC=1.Cl.CN(C)CCCN=C=NCC>CN(C)C=O.CS(C)=O>[Cl:1][C:2]1[C:3]([C:20]2[S:24][C:23]([C:25]3([OH:29])[CH2:28][CH2:27][CH2:26]3)=[N:22][CH:21]=2)=[C:4]2[CH:10]=[C:9]([C:11]3[CH:12]=[CH:13][C:14]([C:15]([N:34]4[CH2:35][CH2:36][N:31]([CH3:30])[CH2:32][CH2:33]4)=[O:17])=[CH:18][CH:19]=3)[NH:8][C:5]2=[N:6][CH:7]=1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 531671-MethylpiperazineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67002710HCID 67002710, compoundHCID 178418300HCID 178418300, compound

Product 1

HCID 67003306HCID 67003306, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of 4-(5-chloro-4-(2-(1-hydroxycyclobutyl)thiazol-5-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)benzoic acid (Example 16C) (100 mg, 0.235 mmol) in N,N-dimethylformamide (1.17 mL) was added 1-methylpiperazine (78 μl, 0.704 mmol), 4-methylmorpholine (71.2 mg, 0.704 mmol), hydroxybenzotriazole (53.9 mg, 0.352 mmol), and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (67.5 mg, 0.352 mmol). The solution was heated to 45° C. for 3 hours. The reaction was cooled to room temperature and diluted with dimethyl sulfoxide (1 mL). The resulting solution was purified by reverse phase high performance liquid chromatography (RP HPLC, 19×150 mm Atlantis Prep T3 OBD 5 m column, eluting with a gradient of 5% B in A to 75% B in A over 25 minutes, wherein A is water containing 0.1% v/v trifluoroacetic acid and B is acetonitrile containing 0.1% v/v trifluoroacetic acid) to give the title compound. 1H NMR (300 MHz, DMSO-d6) δ 12.67 (bs, 1H), 8.37 (s, 1H), 8.28 (s, 1H), 8.10-8.05 (m, 2H), 7.51-7.44 (m, 2H), 7.17 (s, 1H), 6.68 (s, 1H), 3.76-3.48 (m, 4H), 2.69-2.58 (m, 2H), 2.47-2.25 (m, 6H), 2.20 (s, 3H), 2.05-1.91 (m, 2H); MS ESI(+) m/z 508.1 [M+H]+.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. customThe resulting solution was purified by reverse phase high performance liquid chromatography (RP HPLC, 19×150 mm Atlantis Prep T3 OBD 5 m column
  3. washeluting with a gradient of 5% B in A to 75% B in A over 25 minutes

Sources & evidence

ORD record
ord-6e8d7bcd36ec4f31b2d3e2df2c464e40
Source dataset
uspto-grants-2014_04
Patent number
US08691810B2

Reaction notes

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