N-methylcyclopropanamine hydrochloride → Cyclopropyl-(2-methoxymethyl-5,6,7,8-tetrahydro-benzo[4,5]thieno[2,3-d]pyrimidin-4-yl)-methyl-amine

HRID 1056838Notes

Reaction equation

HRID 1056838 reaction equation
Cl[C:2]1[C:3]2[C:13]3[CH2:14][CH2:15][CH2:16][CH2:17][C:12]=3[S:11][C:4]=2[N:5]=[C:6]([CH2:8][O:9][CH3:10])[N:7]=1.Cl.[CH:19]1([NH:22][CH3:23])[CH2:21][CH2:20]1>CO>[CH:19]1([N:22]([C:2]2[C:3]3[C:13]4[CH2:14][CH2:15][CH2:16][CH2:17][C:12]=4[S:11][C:4]=3[N:5]=[C:6]([CH2:8][O:9][CH3:10])[N:7]=2)[CH3:23])[CH2:21][CH2:20]1

Participants

4

Reactant 2

HCID 18546974N-methylcyclopropanamine hydrochlorideHCID 549781034-Chloro-2-methoxymethyl-5,6,7,8-tetrahydro-benzo[4,5]thieno[2,3-d]pyrimidine

Product 1

HCID 89717268Cyclopropyl-(2-methoxymethyl-5,6,7,8-tetrahydro-benzo[4,5]thieno[2,3-d]pyrimidin-4-yl)-methyl-amine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirring suspension of compound 4-Chloro-2-methoxymethyl-5,6,7,8-tetrahydro-benzo[4,5]thieno[2,3-d]pyrimidine (1.0 g, 0.0037 mol) and cyclopropyl methylamine hydrochloride (1.18 g, 0.111 mol) in methanol (100 ml) was added TEA (3.1 ml, 0.022 mol) at 0-5° C. Reaction mixture was then warmed to room temperature and stirred for about 20 h. After completion of the reaction (monitored by TLC) volatilities were removed under vacuum and solid residue obtained was diluted with ice-water solution (200 ml). Aqueous phase was extracted with DCM (2×250 ml). Combined organic layer was washed with brine solution, dried and concentrated on rotary evaporator to get crude material which was purified by prep HPLC to get the desired title compound cyclopropyl-(2-methoxymethyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl)-methyl-amine(N-cyclopropyl-2-(methoxymethyl)-N-methyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-amine) as a yellow solid. Yield: (600 mg, 54.5%); 1H), 2.90-2.87 (m, 2H), 2.83-2.80 (m, 2H), 1.88-1.82 (m, 2H), 1.72-1.68 (m, 2H), 0.76 1H NMR (400 MHz, DMSO) δ ppm=4.41 (s, 2H), 3.36 (s, 3H), 3.30 (s, 3H), 2.97-2.92 (m, −0.70 (m, 2H), 0.40-0.36 (m, 2H); LCMS: [M+H]=304.40; HPLC (purity): 99.61% at 236 nm, 99.45% at 220 nm, 99.32% at 254 nm.

Workup

  1. customReaction mixture
  2. customAfter completion of the reaction (monitored by TLC) volatilities
  3. customwere removed under vacuum and solid residue
  4. customobtained
  5. extractionAqueous phase was extracted with DCM (2×250 ml)
  6. washCombined organic layer was washed with brine solution
  7. customdried
  8. concentrationconcentrated on rotary evaporator
  9. customto get crude material which
  10. customwas purified by prep HPLC

Sources & evidence

ORD record
ord-72a16fa5f76b40cb8094a834e393e75a
Source dataset
uspto-grants-2016_07
Patent number
US09399647B2

Reaction notes

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