4-Methylmorpholine → HCID 66830361, compound

HRID 1040584Notes

Reaction equation

HRID 1040584 reaction equation
[Cl:1][C:2]1[C:3]([NH:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[S:32](=[O:36])(=[O:35])[NH:33][CH3:34])=[N:4][C:5]([NH:8][C:9]2[CH:24]=[CH:23][C:12]3[N:13]([CH2:19][C:20](O)=[O:21])[C:14](=[O:18])[CH2:15][CH2:16][CH2:17][C:11]=3[CH:10]=2)=[N:6][CH:7]=1.[CH3:37][N:38]1[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]1.Cl.CN(C)CCCN=C=NCC.CN1CCOCC1.OC1C2N=NNC=2C=CC=1>CN(C=O)C.CO.C(Cl)Cl>[Cl:1][C:2]1[C:3]([NH:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[S:32]([NH:33][CH3:34])(=[O:36])=[O:35])=[N:4][C:5]([NH:8][C:9]2[CH:24]=[CH:23][C:12]3[N:13]([CH2:19][C:20]([N:41]4[CH2:42][CH2:43][N:38]([CH3:37])[CH2:39][CH2:40]4)=[O:21])[C:14](=[O:18])[CH2:15][CH2:16][CH2:17][C:11]=3[CH:10]=2)=[N:6][CH:7]=1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 531671-MethylpiperazineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67263936HCID 67263936, compoundHCID 178418300HCID 178418300, compound

Product 1

HCID 66830361HCID 66830361, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

{7-[5-Chloro-4-(2-methylsulfamoyl-phenylamino)-pyrimidin-2-ylamino]-2-oxo-2,3,4,5-tetrahydro-benzo[b]azepin-1-yl}-acetic acid (227 mg, 0.43 mmol), N-methylpiperazine (48 μl, 0.43 mmol), 1-[3-(dimethylamino)propyl]3-ethylcarbodiimide hydrochloride (98 mg, 0.51 mmol), N-methylmorpholine (119 μl, 2.5 mmol), and hydroxybenzotriazole (69 mg, 0.51 mmol) were dissolved in anhydrous DMF, and the solution was stirred 18 hours at room temperature. It was then partitioned between ethyl acetate and water, and washed once with aqueous sodium bicarbonate and once with water. Concentration afforded a yellow foam. Preparative TLC (10% MeOH/CH2Cl2) gave 2-(5-Chloro-2-{1-[2-(4-methyl-piperazin-1-yl)-2-oxo-ethyl]-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamino}-pyrimidin-4-ylamino)-N-methyl-benzenesulfonamideas a white solid, 147 mg. (56% yield) 1H NMR (400 MHz, DMSO-d6) δ 9.51 (s, 1H), 9.27 (s, 1H), 8.43-8.51 (m, 1H), 8.23 (s, 1H), 7.70-7.83 (m, 2H), 7.58-7.64 (m, 1H), 7.41-7.48 (m, 2H), 7.23-7.30 (m, 1H), 7.08-7.12 (m, 1H), 4.58 (s, 2H), 3.34-3.43 (m, 4H), 2.62-3.10 (m, 2H), 2.39 (s, 3H), 1.96-2.32 (m, 11H); MS (m/e) 613 (M+1); retention time 5.99 minute; mp 148-151° C.

Workup

  1. customIt was then partitioned between ethyl acetate and water
  2. washwashed once with aqueous sodium bicarbonate and once with water
  3. concentrationConcentration
  4. customafforded a yellow foam

Sources & evidence

ORD record
ord-dfd9cbf6db344f19b2bfe13bdca6d024
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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