Dimethylamine → HCID 122512301, compound

HRID 1479103Notes

Reaction equation

HRID 1479103 reaction equation
[Cl:1][C:2]1[C:10]([CH3:11])=[N:9][C:8]2[N:4]([N:5]=[C:6]3[CH2:14][N:13]([C:15]([C:17]4[CH:27]=[CH:26][CH:25]=[CH:24][C:18]=4[O:19][CH:20]([CH3:23])[CH:21]=O)=[O:16])[CH2:12][C:7]3=2)[C:3]=1[CH3:28].[CH3:29][NH:30][CH3:31].C1COCC1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.C(Cl)Cl>[ClH:1].[Cl:1][C:2]1[C:10]([CH3:11])=[N:9][C:8]2[N:4]([N:5]=[C:6]3[CH2:14][N:13]([C:15]([C:17]4[CH:27]=[CH:26][CH:25]=[CH:24][C:18]=4[O:19][CH:20]([CH3:23])[CH2:21][N:30]([CH3:31])[CH3:29])=[O:16])[CH2:12][C:7]3=2)[C:3]=1[CH3:28]

Participants

7

Reactant 4

HCID 674DimethylamineHCID 8028TetrahydrofuranHCID 5049666Sodium triacetoxyborohydrideHCID 131736561HCID 131736561, compound

Product 1

HCID 122512301HCID 122512301, compoundYield 20%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-[2-(6-chloro-5,7-dimethyl-1H,3H-2,4,7a,8-tetraaza-cyclopenta[a]indene-2-carbonyl)-phenoxy]-propionaldehyde (170 mg; 0.43 mmol; 1 eq.), a 1M solution of dimethyl-amine in THF (2.1 mL; 2.1 mmol; 5 eq.) and sodium triacetoxyborohydride (117 mg; 0.55 mmol; 1.3 eq.) in DCE (10 mL) was stirred at 70° C. for 16 hours. The solution was diluted with DCM, washed with sat. aq. NaHCO3 then brine, dried over magnesium sulfate and concentrated in vacuo. Purification by column chromatography (DCM to 20% MeOH in DCM) followed by hydrochloride formation with a 4M solution of HCl in 1,4-dioxane and crystallization from hot MTBE afforded the title compound (40 mg, 20%) as a pale yellow solid. 1H NMR (DMSO-d6) δ 9.83 (br s, 1H), 7.54-7.45 (m, 1H), 7.41 (ddd, J=7.6, 3.9, 1.7 Hz, 1H), 7.26 (d, J=8.5 Hz, 1H), 7.13 (t, J=7.4 Hz, 1H), 5.04-4.91 (m, 1H), 4.90-4.80 (d, J=7.9 Hz, 2H), 4.71-4.41 (m, 2H), 2.85 (s, 1.5H), 2.82 (s, 1.5H), 2.75 (br s, 6H), 2.63 (s, 1.5H), 2.56 (s, 1.5H), 1.30-1.22 (m, 3H). HPLC (max plot) 98.7%, Rt 2.79 min. UPLC/MS: (MS+) 428.3 ([M+H]+).

Workup

  1. washwashed with sat. aq. NaHCO3
  2. dry with materialbrine, dried over magnesium sulfate
  3. concentrationconcentrated in vacuo
  4. customPurification by column chromatography (DCM to 20% MeOH in DCM)
  5. customfollowed by hydrochloride formation with a 4M solution of HCl in 1,4-dioxane and crystallization from hot MTBE

Sources & evidence

ORD record
ord-dc7f8e286e934108b7b7484d6b46dcb4
Source dataset
uspto-grants-2016_08
Patent number
US09403835B2

Reaction notes

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