4-Methylmorpholine → HCID 67995603, compound

HRID 2361380Notes

Reaction equation

HRID 2361380 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][N:7]([C:12]3[C:13]([CH3:39])=[C:14]([C:18]4[C:30]5[C:29]6[CH:28]=[CH:27][C:26]([O:31][CH2:32][CH2:33][O:34][CH3:35])=[CH:25][C:24]=6[NH:23][C:22]=5[C:21]([C:36](O)=[O:37])=[N:20][N:19]=4)[CH:15]=[CH:16][CH:17]=3)[C:8]2=[O:11])=[CH:4][CH:3]=1.[Cl-].[NH4+].CC[N:44](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.CO>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][N:7]([C:12]3[C:13]([CH3:39])=[C:14]([C:18]4[C:30]5[C:29]6[CH:28]=[CH:27][C:26]([O:31][CH2:32][CH2:33][O:34][CH3:35])=[CH:25][C:24]=6[NH:23][C:22]=5[C:21]([C:36]([NH2:44])=[O:37])=[N:20][N:19]=4)[CH:15]=[CH:16][CH:17]=3)[C:8]2=[O:11])=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 67994607HCID 67994607, compound

Product 1

HCID 67995603HCID 67995603, compoundYield 31.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

A yellow, homogeneous solution of 1-(3-(6-chloro-1-oxoisoindolin-2-yl)-2-methylphenyl)-7-(2-methoxyethoxy)-5H-pyridazino[4,5-b]indole-4-carboxylic acid (0.0206 g, 0.038 mmol), ammonium chloride (8.12 mg, 0.152 mmol), DIPEA (0.032 mL, 0.182 mmol), N-methylmorpholine (5.42 μL, 0.049 mmol) and BOP (0.065 g, 0.148 mmol) in DMF (0.379 mL) was stirred for 1 hr. It was diluted with MeOH (1 mL) and purified by reverse phase HPLC. The appropriate fractions were collected, basified with NaHCO3 (solid), and concentrated in vacuo. The residue was extracted with CH2Cl2 (3×). The combined extract was dried over Na2SO4 and concentrated in vacuo to give the desired product (0.0064 g, 0.012 mmol, 30.9% yield) as a white solid. LC/MS (M+H)=542.15; 1H NMR (500 MHz, DMSO-d6) (recognizable peaks for major atropoisomer) δ ppm 12.22 (s, 1H), 8.71 (s, 1H), 7.98 (s, 1H), 7.80-7.85 (m, 1H), 7.74-7.76 (m, 2H), 7.73 (d, J=1.1 Hz, 1H), 7.58 (s, 1H), 7.53 (d, J=1.1 Hz, 1H), 7.41 (d, J=2.2 Hz, 1H), 7.19 (d, J=8.9 Hz, 1H), 6.87 (d, J=2.2 Hz, 1H), 5.05 (d, J=17.8 Hz, 1H), 4.98 (d, J=17.5 Hz, 1H), 4.14-4.21 (m, 2H), 3.72 (dd, J1=5.4 Hz, J2=3.8 Hz, 2H), 3.32 (s, 3 H), 1.88 (s, 3 H).

Workup

  1. custompurified by reverse phase HPLC
  2. customThe appropriate fractions were collected
  3. concentrationconcentrated in vacuo
  4. extractionThe residue was extracted with CH2Cl2 (3×)
  5. extractionThe combined extract
  6. dry with materialwas dried over Na2SO4
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d0384f1434a1417d8e1a47fb25a124a0
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

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