4-Methylmorpholine → HCID 50923462, compound

HRID 241405Notes

Reaction equation

HRID 241405 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:9]=[N:10][N:11]([CH2:13][C:14]([OH:16])=O)[CH:12]=2)=[CH:4][C:3]=1[C:17]1[NH:21][C:20]2[CH:22]=[C:23]([O:26][CH3:27])[CH:24]=[CH:25][C:19]=2[N:18]=1.[F:28][C:29]1[CH:30]=[C:31]([CH:34]=[CH:35][C:36]=1[F:37])[CH2:32][NH2:33].C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1>CN(C=O)C.O.C(OCC)(=O)C.C(Cl)CCl>[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:9]=[N:10][N:11]([CH2:13][C:14]([NH:33][CH2:32][C:31]3[CH:34]=[CH:35][C:36]([F:37])=[C:29]([F:28])[CH:30]=3)=[O:16])[CH:12]=2)=[CH:4][C:3]=1[C:17]1[NH:21][C:20]2[CH:22]=[C:23]([O:26][CH3:27])[CH:24]=[CH:25][C:19]=2[N:18]=1

Participants

8

Reactant 4

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 1235723,4-DifluorobenzylamineHCID 66887349HCID 66887349, compound

Product 1

HCID 50923462HCID 50923462, compound

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 6228DimethylformamideSolventHCID 22728543Water ethylacetateSolvent

Procedure

4a.2 146 mg of {4-[6-amino-5-(6-methoxy-1H-benzimidazol-2-yl)pyridin-3-yl]pyrazol-1-yl}acetic acid (0.120 mmol) are dissolved in 1.5 ml of DMF. 17.5 mg (0.120 mmol) of 3,4-difluorobenzylamine, 16.2 mg (0.120 mmol) of HOBt, 23 mg (0120 mmol) of EDC and 26.4 μl (0.240 mmol) of N-methylmorpholine are added. The reaction mixture is stirred at room temperature for 14 h, and water/ethyl acetate is subsequently added. The aqueous phase is extracted 2× with ethyl acetate. The combined organic phases are washed with water, dried using sodium sulfate, filtered and evaporated to dryness. The residue is purified by means of preparative RP-HPLC, giving 2-{4-[6-amino-5-(6-methoxy-1H-benzimidazol-2-yl)pyridin-3-yl]pyrazol-1-yl}-N-(3,4-difluorobenzyl)acetamide; HPLC-MS [M+H]+ 490.2;

Workup

  1. extractionThe aqueous phase is extracted 2× with ethyl acetate
  2. washThe combined organic phases are washed with water
  3. customdried
  4. filtrationfiltered
  5. customevaporated to dryness
  6. customThe residue is purified by means of preparative RP-HPLC

Sources & evidence

ORD record
ord-531eab012d124fa88d7ea7b7adc7b14c
Source dataset
uspto-grants-2014_02
Patent number
US08648201B2

Reaction notes

Loading…