4-Methylmorpholine → HCID 67995228, compound

HRID 2361317Notes

Reaction equation

HRID 2361317 reaction equation
[Si:1]([O:8][CH:9]1[CH2:13][CH2:12][N:11]([C:14]2[CH:22]=[C:21]3[C:17]([C:18]4[C:26]([C:27]5[C:28]([CH3:45])=[C:29]([NH:33][CH2:34][C:35]6[CH:43]=[CH:42][C:41]([Cl:44])=[CH:40][C:36]=6[C:37](O)=[O:38])[CH:30]=[CH:31][CH:32]=5)=[CH:25][N:24]=[C:23]([C:46](=[O:48])[NH2:47])[C:19]=4[NH:20]3)=[CH:16][CH:15]=2)[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].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>[Si:1]([O:8][CH:9]1[CH2:13][CH2:12][N:11]([C:14]2[CH:22]=[C:21]3[C:17]([C:18]4[C:26]([C:27]5[CH:32]=[CH:31][CH:30]=[C:29]([N:33]6[CH2:34][C:35]7[C:36](=[CH:40][C:41]([Cl:44])=[CH:42][CH:43]=7)[C:37]6=[O:38])[C:28]=5[CH3:45])=[CH:25][N:24]=[C:23]([C:46]([NH2:47])=[O:48])[C:19]=4[NH:20]3)=[CH:16][CH:15]=2)[CH2:10]1)([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 67994863HCID 67994863, compound

Product 1

HCID 67995228HCID 67995228, compoundYield 45%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 2-((3-(7-(3-(tert-butyldimethylsilyloxy)pyrrolidin-1-yl)-1-carbamoyl-9H-pyrido[3,4-b]indol-4-yl)-2-methylphenylamino)methyl)-5-chlorobenzoic acid (0.104 g, 0.152 mmol), DIPEA (0.080 mL, 0.456 mmol), N-methylmorpholine (0.134 mL, 1.216 mmol) and BOP (0.175 g, 0.395 mmol) in DMF (1.520 mL) under nitrogen was heated at 45° C. for 1 h. 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, filtered and concentrated in vacuo to give a residue which was purified by flash chromatography using an ISCO 12 g column eluting with 0-20 EtOAc/hexanes. Appropriate fractions were collected and concentrated in vacuo to give the desired product (0.0456 g, 0.068 mmol, 45.0% 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. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto give a residue which
  6. customwas purified by flash chromatography
  7. washeluting with 0-20 EtOAc/hexanes
  8. customAppropriate fractions were collected
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a1129a0117ab42c69d747fd2f72b692a
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

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