Formaldehyde → HCID 57526732, compound

HRID 1394898Notes

Reaction equation

HRID 1394898 reaction equation
[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:37]([NH:39][S:40]([N:43]([CH3:45])[CH3:44])(=[O:42])=[O:41])=[O:38])=[CH:12][C:13]=3[N:14]3[CH2:20][C:19]([C:21]([N:23]4[CH2:28][C@H:27]([CH3:29])[NH:26][C@H:25]([CH3:30])[CH2:24]4)=[O:22])=[CH:18][C:17]4[CH:31]=[C:32]([O:35][CH3:36])[CH:33]=[CH:34][C:16]=4[C:15]=23)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C=O.[C:48]([BH3-])#N.[Na+]>CO.[Cl-].[Zn+2].[Cl-]>[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:37]([NH:39][S:40]([N:43]([CH3:44])[CH3:45])(=[O:41])=[O:42])=[O:38])=[CH:12][C:13]=3[N:14]3[CH2:20][C:19]([C:21]([N:23]4[CH2:24][C@H:25]([CH3:30])[N:26]([CH3:48])[C@H:27]([CH3:29])[CH2:28]4)=[O:22])=[CH:18][C:17]4[CH:31]=[C:32]([O:35][CH3:36])[CH:33]=[CH:34][C:16]=4[C:15]=23)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 69206430HCID 69206430, compound

Product 1

HCID 57526732HCID 57526732, compoundYield 82%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 13-cyclohexyl-N-[(dimethylamino)sulfonyl]-6-[(cis-3,5-dimethyl-1-piperazinyl)carbonyl]-3-methoxy-7H-indolo[2,1-a][2]benzazepine-10-carboxamide (42 mg, 0.066 mmol), zinc chloride (27.4 mg, 0.20 mmol), paraformaldehyde (6.0 mg, 0.20 mmol), and sodium cyanoborohydride (12.7 mg, 0.20 mmol) in MeOH was heated at 60° C. for 2 hrs. The mixture was quenched with 0.5 mL of NaOH (1N). The solution was extracted with ethyl acetate and the extract washed with dilute sodium bicarbonate (2×), brine (3×), and then dried (Na2SO4). The extract was concentrated and the crude product purified on the Shimadzu preparative liquid chromatograph. The product containing fraction was concentrated on a Speed Vac® to leave, the titled compound as a yellow solid (35 mg, 82%). ESI-MS m/z 648 (MH+); 1H NMR (500 MHz, CHLOROFORM-D) δ ppm 0.77-1.58 (m, 10 H) 1.69-2.19 (m, 6 H) 2.76-2.91 (m, 4 H) 3.01 (s, 6 H) 3.12-3.38 (m, 5 H) 3.91 (s, 3 H) 4.33-4.49 (m, 2 H) 5.07-5.22 (m, 1 H) 6.99 (s, 1 H) 7.08 (d, J=2.44 Hz, 1 H) 7.16 (dd, J=8.70, 2.59 Hz, 1 H) 7.56 (t, J=9.31 Hz, 2 H) 7.93 (d, J=8.55 Hz, 1 H) 8.11 (s, 1 H).

Workup

  1. customThe mixture was quenched with 0.5 mL of NaOH (1N)
  2. extractionThe solution was extracted with ethyl acetate
  3. washthe extract washed with dilute sodium bicarbonate (2×), brine (3×)
  4. dry with materialdried (Na2SO4)
  5. concentrationThe extract was concentrated
  6. customthe crude product purified on the Shimadzu preparative liquid chromatograph
  7. additionThe product containing fraction
  8. concentrationwas concentrated on a Speed Vac®
  9. customto leave

Sources & evidence

ORD record
ord-b95dbef5522442fba1efeba8bf12cced
Source dataset
uspto-grants-2008_03
Patent number
US07348425B2

Reaction notes

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