Acetic Acid → HCID 68698137, compound

HRID 1444621Notes

Reaction equation

HRID 1444621 reaction equation
[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:33]([O:35][CH3:36])=[O:34])=[CH:12][C:13]=3[N:14]3[CH2:20][CH2:19][CH:18]([NH:21][CH2:22][CH2:23][N:24]4[CH2:28][CH2:27][CH2:26][CH2:25]4)[C:17]4[CH:29]=[CH:30][CH:31]=[CH:32][C:16]=4[C:15]=23)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:37]C(O)=O.C=O.[BH3-]C#N.[Na+]>C(Cl)Cl.CCOC(C)=O>[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:33]([O:35][CH3:36])=[O:34])=[CH:12][C:13]=3[N:14]3[CH2:20][CH2:19][CH:18]([N:21]([CH3:37])[CH2:22][CH2:23][N:24]4[CH2:28][CH2:27][CH2:26][CH2:25]4)[C:17]4[CH:29]=[CH:30][CH:31]=[CH:32][C:16]=4[C:15]=23)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 68697362HCID 68697362, compound

Product 1

HCID 68698137HCID 68698137, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Methyl 13-cyclohexyl-5-[(2-pyrrolidin-1-ylethyl)amino]-6,7-dihydro-5H-indolo[2,1-a][2]benzazepine-10-carboxylate (prepared as in Example 3) was dissolved in DCM and the pH adjusted to 6 with AcOH; 37% aq HCHO and, after 30 min NaCNBH3 (3 eq), were added and the mixture was stirred at RT overnight. The reaction mixture was diluted with EtOAc and washed with IN NaOH and brine, dried and evaporated affording methyl 13-cyclohexyl-5-[methyl(2-pyrrolidin-1-ylethyl)amino]-6,7-dihydro-5H-indolo[2,1-a][2]benzazepine-10-carboxylate. Hydrolysis of the foregoing methyl ester was done with IM aqueous KOH (6 eq) in dioxane (0.1M) at 60 ° C.; the reaction was complete in 2 h, and the title compound was obtained in 29% yield after RP-HPLC purification and lyophilisation (Conditions: Column: Waters X-TERRA MS C18, 10 micron, 19×150 mm; Gradient: A: H2O+0.1% TFA; B: MeCN+0.1% TFA; 75% A isocratic for 3 min, linear to 20% A in 12 min).

Workup

  1. additionwere added
  2. washwashed with IN NaOH and brine
  3. customdried
  4. customevaporated

Sources & evidence

ORD record
ord-4dceff8893f14d759355df78927bdc54
Source dataset
uspto-grants-2010_02
Patent number
US07662809B2

Reaction notes

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