4-Methylmorpholine → HCID 86601024, compound

HRID 2220674Notes

Reaction equation

HRID 2220674 reaction equation
[C:1]([C:3]1[CH:11]=[C:10]2[C:6]([C:7]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([C:21](=[O:28])[NH:22][CH2:23][C:24](=[O:27])[NH:25][CH3:26])=[CH:17][C:16]=3[C:29]3[C:30]([C:36]([OH:38])=[O:37])=[CH:31][C:32]([CH3:35])=[CH:33][CH:34]=3)=[CH:8][N:9]2CC)=[CH:5][CH:4]=1)#[N:2].[C:39]([C:42]1C=C2C(C(CC3C=CC(C(=O)NCC4C=NC=CC=4)=CC=3C3C(C(O)=O)=CC(C)=CC=3)=CN2CC)=CC=1)(=N)N.C[NH:81]C(=O)CN.CN1CCOCC1.CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O>[C:1]([C:3]1[CH:11]=[C:10]2[C:6]([C:7]([CH:14]([CH2:39][CH3:42])[C:15]3[CH:20]=[CH:19][C:18]([C:21](=[O:28])[NH:22][CH2:23][C:24](=[O:27])[NH:25][CH3:26])=[CH:17][C:16]=3[C:29]3[C:30]([C:36]([OH:38])=[O:37])=[CH:31][C:32]([CH3:35])=[CH:33][CH:34]=3)=[CH:8][NH:9]2)=[CH:5][CH:4]=1)(=[NH:2])[NH2:81]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 896752-amino-N-methylacetamideHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 11606358HCID 11606358, compoundHCID 69198267HCID 69198267, compound

Product 1

HCID 86601024HCID 86601024, compoundYield 85%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Part A. 2′-(6-cyano-1-ethyl-1H-indol-3-ylmethyl)-4-methyl-5′-(methylcarbamoylmethyl-carbamoyl)-biphenyl-2-carboxylic acid: A solution of the compound of Example 37, Part D (0.1 g, 0.19 mmol), N-methylglycinamide (0.04 mg, 0.28 mmole), NMM (0.1 ml, 0.9 mmol) and BOP reagent (0.13 g, 0.28 mmol) in 1.5 ml DMF was stirred for 3 days at rt in a screw cap test tube. Reaction was diluted with water and extracted 3× with EtOAc. Combined extracts were washed with water and brine then dried over anh. Na2SO4, filtered and evaporated. Chromatography on silica gel provided the amide product (99 mg. 85%). 1H NMR (500 MHz, CDCl3) δ ppm 1.37 (t, J=7.15 Hz, 3H) 2.41 (s, 3H) 2.83 (d, J=4.40 Hz, 3H) 3.77 (s, 2H) 4.03 (m, 4H) 6.06 (s, 1H) 6.66 (s, 1H) 6.75 (t, J=5.22 Hz, 1H) 6.97 (d, J=7.70 Hz, 1H) 7.05 (m, 2H) 7.17 (dd, J=15.95, 8.25 Hz, 2H) 7.24 (m, 5H) 7.50 (s, 1H) 7.56 (s, 1H) 7.64 (d, J=6.05 Hz, 1H) 7.83 (s, 1H). LC/MS m/z 599.4)M+H)+.

Workup

  1. customcap test tube
  2. customReaction
  3. extractionextracted 3× with EtOAc
  4. washCombined extracts were washed with water and brine
  5. dry with materialthen dried over anh. Na2SO4
  6. filtrationfiltered
  7. customevaporated

Sources & evidence

ORD record
ord-7f70073bd58c45989028c7dcc7f36e8a
Source dataset
uspto-grants-2008_08
Patent number
US07417063B2

Reaction notes

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