Sodium Hydroxide → HCID 57559087, compound

HRID 1723950Notes

Reaction equation

HRID 1723950 reaction equation
[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:31](=[O:39])[NH:32][S:33]([N:36]([CH3:38])[CH3:37])(=[O:35])=[O:34])=[CH:12][C:13]=3[N:14]3[CH2:20][C:19]([C:21](OC)=[O:22])=[CH:18][C:17]4[CH:25]=[C:26]([O:29][CH3:30])[CH:27]=[CH:28][C:16]=4[C:15]=23)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[OH-].[Na+].[CH3:42][N:43]([CH3:48])[CH2:44][CH2:45][NH:46][CH3:47].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O.Cl.C(N(CC)CC)C.CO>[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:31]([NH:32][S:33]([N:36]([CH3:38])[CH3:37])(=[O:35])=[O:34])=[O:39])=[CH:12][C:13]=3[N:14]3[CH2:20][C:19]([C:21]([N:46]([CH2:45][CH2:44][N:43]([CH3:48])[CH3:42])[CH3:47])=[O:22])=[CH:18][C:17]4[CH:25]=[C:26]([O:29][CH3:30])[CH:27]=[CH:28][C:16]=4[C:15]=23)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

10

Reactant 4

HCID 14798Sodium HydroxideHCID 673381,2-Ethanediamine, N1,N1,N2-trimethyl-HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59682124HCID 59682124, compound

Product 1

HCID 57559087HCID 57559087, compoundYield 121.6%

Reagents, catalysts & solvents 5

HCID 313Hydrochloric AcidSolvent2×HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
80 °C

Procedure

Methyl 13-cyclohexyl-10-(((dimethylamino)sulfonyl)carbamoyl)-3-methoxy-7H-indolo[2,1-a][2]benzazepine-6-carboxylate (700 mg, 1.27 mmol) was dissolved into MeOH//THF (1:1, 14 mL) and treated with 1M aqueous NaOH (3 mL). The reaction mixture was stirred and heated at 80° C. with microwave irradiation for 15 min and cooled to rt. The clear solution was neutralized with 1M aqueous HCl (3 mL) and concentrated to remove organic solvents. The residue was stirred with H2O (10 mL) for 1 h and the resultant solids were collected by filtration, washed with H2O and dried under vacuum. To a solution of these solids, N1,N1,N2-trimethylethane-1,2-diamine (191 mg, 1.88 mmol) and triethylamine (0.700 mL) in DMF (5 mL) was added HATU (620 mg, 1.63 mmol). The reaction mixture was stirred at rt for 1 h, diluted with H2O (25 mL) and 1M HCl (aq.) (5 mL) and stirred 20 The precipitates were collected by filtration, rinsed with H2O and dried to yield impure 13-cyclohexyl-N6-(2-(dimethylamino)ethyl)-N10-((dimethylamino)sulfonyl)-3-methoxy-N6-methyl-7H-indolo[2,1-a][2]benzazepine-6,10-dicarboxamide (960 mg) as a yellow powder. A crude sample of 13-cyclohexyl-N6-(2-(dimethylamino)ethyl)-N10-((dimethylamino)sulfonyl)-3-methoxy-N6-methyl-7H-indolo[2,1-a][2]benzazepine-6,10-dicarboxamide (100 mg) was dissolved into MeOH/DMF (3:1, 4 mL), filtered and purified by preparative HPLC (H2O/CH3CN with 10 mM NH4OAc buffer) to yield 13-cyclohexyl-N6-(2-(dimethylamino)ethyl)-N10-((dimethylamino)sulfonyl)-3-methoxy-N6-methyl-7H-indolo[2,1-a][2]benzazepine-6,10-dicarboxamide (78 mg, 0.13 mmol, 95%) 1HNMR (300 MHz, CD3OD) δ 1.11-3.07 (m, 24H), 2.99 (s, 6H), 3.50-3.76 (m, 2H), 3.93 (s, 3H), 4.27-4.44 (m, 1H), 5.05-5.25 (m, 1H), 7.05 (s, 1H) 7.08 (d, J=2.6 Hz, 1H), 7.16 (dd, J=8.8, 2.6 Hz, 1H), 7.56 (d, J=8.4 Hz, 1H), 7.64 (dd, J=8.8, 1.5 Hz, 1H), 7.88 (d, J=8.4 Hz, 1H), 8.16 (br s, 1H). LCMS: m/e 620 (M−H)−, ret time 2.32 min, column A, 4 minute gradient.

Workup

  1. temperaturecooled to rt
  2. concentrationconcentrated
  3. customto remove organic solvents
  4. stirringThe residue was stirred with H2O (10 mL) for 1 h
  5. filtrationthe resultant solids were collected by filtration
  6. washwashed with H2O
  7. customdried under vacuum
  8. stirringThe reaction mixture was stirred at rt for 1 h
  9. stirringstirred 20 The precipitates
  10. filtrationwere collected by filtration
  11. washrinsed with H2O
  12. customdried

Sources & evidence

ORD record
ord-f4d4c9d9a1bd47d59d44a0533e0a7931
Source dataset
uspto-grants-2009_02
Patent number
US07485633B2

Reaction notes

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