Pyrrolidine → HCID 56644015, compound

HRID 1526690Notes

Reaction equation

HRID 1526690 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:14]3[CH:15]=[C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[C:21]([CH:25]=O)[CH:20]=4)[CH:17]=[CH:18][C:13]=3[N:12]3[C:27]([CH3:30])=[N:28][N:29]=[C:11]3[C@H:10]([CH2:31][C:32]([NH:34][CH2:35][CH3:36])=[O:33])[N:9]=2)=[CH:4][CH:3]=1.[NH:37]1[CH2:41][CH2:40][CH2:39][CH2:38]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>C(Cl)Cl.C(O)(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:14]3[CH:15]=[C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[C:21]([CH2:25][N:37]5[CH2:41][CH2:40][CH2:39][CH2:38]5)[CH:20]=4)[CH:17]=[CH:18][C:13]=3[N:12]3[C:27]([CH3:30])=[N:28][N:29]=[C:11]3[C@H:10]([CH2:31][C:32]([NH:34][CH2:35][CH3:36])=[O:33])[N:9]=2)=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 31268PyrrolidineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 86679714HCID 86679714, compound

Product 1

HCID 56644015HCID 56644015, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Procedure

(S)-2-(6-(4-Chlorophenyl)-8-(3-formylphenyl)-1-methyl-4H-benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepin-4-yl)-N-ethylacetamide (for a preparation see Intermediate 5) (95 mg) was dissolved in DCM (5 ml). Pyrrolidine (24 μl) and acetic acid (8.62 μl) were added and the reaction mixture was stirred for 5 min. Sodium triacetoxyborohydride (202 mg) was added and the reaction mixture was stirred at room temperature, under nitrogen, overnight. Saturated sodium hydrogen carbonate solution (5 ml) was added and the reaction mixture was stirred for 10 min. The organic phase was separated and the saturated sodium hydrogen carbonate solution was extracted with DCM (10 ml). The DCM extracts were combined, dried and the solvent was evaporated. The residue was chromatographed (0-15% methanol:DCM), triturated with diethyl ether and dried in a vacuum dessicator at 40° C. over the weekend to give (S)-2-(6-(4-chlorophenyl)-1-methyl-8-(3-(pyrrolidin-1-ylmethyl)phenyl)-4H-benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepin-4-yl)-N-ethylacetamide (71.7 mg) as a white solid. LCMS (formate): MH+ 553/555, RT 0.76 min

Workup

  1. stirringthe reaction mixture was stirred at room temperature, under nitrogen, overnight
  2. stirringthe reaction mixture was stirred for 10 min
  3. customThe organic phase was separated
  4. extractionthe saturated sodium hydrogen carbonate solution was extracted with DCM (10 ml)
  5. customdried
  6. customthe solvent was evaporated
  7. customThe residue was chromatographed (0-15% methanol:DCM)
  8. customtriturated with diethyl ether
  9. customdried in a vacuum dessicator at 40° C. over the weekend

Sources & evidence

ORD record
ord-1ac78db0f9af44608478333d8350f423
Source dataset
uspto-grants-2015_07
Patent number
US09085582B2

Reaction notes

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