Acetic Acid → (7-Chloro-thieno[3,2-b]pyridin-2-yl)-(6-dimethylamino-3-aza-bicyclo[3.1.0]hex-3-yl)-methanone

HRID 1063216Notes

Reaction equation

HRID 1063216 reaction equation
[BH3-][C:2]#[N:3].[Na+].N[CH:6]1[CH:11]2[CH:7]1[CH2:8][N:9]([C:12]([C:14]1[S:22][C:21]3[C:16](=[N:17][CH:18]=[CH:19][C:20]=3[Cl:23])[CH:15]=1)=[O:13])[CH2:10]2.C=O.[CH3:26]C(O)=O>CC#N>[Cl:23][C:20]1[CH:19]=[CH:18][N:17]=[C:16]2[CH:15]=[C:14]([C:12]([N:9]3[CH2:10][CH:11]4[CH:7]([CH:6]4[N:3]([CH3:2])[CH3:26])[CH2:8]3)=[O:13])[S:22][C:21]=12

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 22278660(6-Amino-3-aza-bicyclo[3.1.0]hex-3-yl)-(7-chloro-thieno[3,2-b]pyridin-2-yl)-methanone

Product 1

HCID 22278613(7-Chloro-thieno[3,2-b]pyridin-2-yl)-(6-dimethylamino-3-aza-bicyclo[3.1.0]hex-3-yl)-methanoneYield 16%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

NaBH3CN (211 mg, 3.36 mmol) was added to a solution of (6-amino-3-aza-bicyclo[3.1.0]hex-3-yl)-(7-chloro-thieno[3,2-b]pyridin-2-yl)-methanone (250 mg, 0.85 mmol) and formaldehyde (1.14 mL, 17 mmol) in CH3CN at 0° C. After 30 min AcOH (0.5 mL) was added and the reaction mixture was allowed to warm to room temperature. After 1 h the reaction mixture was concentrated, and the resulting residue was dissolved in H20. The resulting aqueous layer was adjusted to pH 9 with 6N NaOH. The resulting solution was extracted with CH2Cl2 (2×) and the combined organic extracts were dried over Na2SO4, filtered, then concentrated. The resulting material was purified on silica gel by flash column chromatography CH2Cl2/MeOH (85/15) to afford the title compound as a white solid (44 mg, 16%). MS: 322.2/324.2 (MH+); HPLC Rf: 3.62 min.; HPLC purity 95%.

Workup

  1. concentrationAfter 1 h the reaction mixture was concentrated
  2. dissolutionthe resulting residue was dissolved in H20
  3. extractionThe resulting solution was extracted with CH2Cl2 (2×)
  4. dry with materialthe combined organic extracts were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resulting material was purified on silica gel by flash column chromatography CH2Cl2/MeOH (85/15)

Sources & evidence

ORD record
ord-856601517c5d4c1db80d416bdd335280
Source dataset
uspto-grants-2005_11
Patent number
US06964961B2

Reaction notes

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