4-Methylmorpholine → HCID 67995327, compound

HRID 2361323Notes

Reaction equation

HRID 2361323 reaction equation
[C:1]([C:4]1[C:9]2[NH:10][C:11]3[C:16]([C:8]=2[C:7]([C:27]2[C:28]([CH3:45])=[C:29]([NH:33][CH2:34][C:35]4[CH:43]=[CH:42][C:41]([Cl:44])=[CH:40][C:36]=4[C:37]([OH:39])=O)[CH:30]=[CH:31][CH:32]=2)=[CH:6][N:5]=1)=[CH:15][CH:14]=[C:13]([NH:17][C:18]([O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])=[O:19])[CH:12]=3)(=[O:3])[NH2:2].CCN(C(C)C)C(C)C.CN1CCOCC1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C=O)C.CCOC(C)=O>[C:1]([C:4]1[C:9]2[NH:10][C:11]3[C:16]([C:8]=2[C:7]([C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([N:33]4[CH2:34][C:35]5[C:36](=[CH:40][C:41]([Cl:44])=[CH:42][CH:43]=5)[C:37]4=[O:39])[C:28]=2[CH3:45])=[CH:6][N:5]=1)=[CH:15][CH:14]=[C:13]([NH:17][C:18](=[O:19])[O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[CH:12]=3)(=[O:3])[NH2:2]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 67994770HCID 67994770, compound

Product 1

HCID 67995327HCID 67995327, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 2-((3-(1-carbamoyl-7-((2-(trimethylsilyl)ethoxy)carbonylamino)-9H-pyrido[3,4-b]indol-4-yl)-2-methylphenylamino)methyl)-5-chlorobenzoic acid (0.343 g, 0.533 mmol), DIPEA (0.279 mL, 1.599 mmol), N-methylmorpholine (0.469 mL, 4.26 mmol) and BOP (0.613 g, 1.386 mmol) in DMF (5.33 mL) under nitrogen was heated at 45° C. for 45 min. The reaction was cooled to room temperature, dissolved in EtOAc (100 mL) and washed with water (3×25 mL) and brine (25 mL), dried over MgSO4, and concentrated in vacuo to give a residue which was purified by flash chromatography using an ISCO 40 g column eluting with 30-75% EtOAc/hexanes. Appropriate fractions were collected and concentrated in vacuo to give the desired product (0.140 g, 0.224 mmol, 41.9% yield) as a light orange solid.

Workup

  1. washwashed with water (3×25 mL) and brine (25 mL)
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated in vacuo
  4. customto give a residue which
  5. customwas purified by flash chromatography
  6. washeluting with 30-75% EtOAc/hexanes
  7. customAppropriate fractions were collected
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6d3f40086e8a49f3aabb7e19e8fc0bcd
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

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