1-Hydroxybenzotriazole → 2-(4-(cyclopropyl(methyl)amino)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-2-yl)-N,N-dimethylacetamide

HRID 1056835Notes

Reaction equation

HRID 1056835 reaction equation
[CH:1]1([N:4]([CH3:22])[C:5]2[C:6]3[C:17]4[CH2:18][CH2:19][CH2:20][CH2:21][C:16]=4[S:15][C:7]=3[N:8]=[C:9]([CH2:11][C:12](O)=[O:13])[N:10]=2)[CH2:3][CH2:2]1.C1C=CC2N(O)N=NC=2C=1.C[CH2:34][N:35]=[C:36]=NCCCN(C)C.Cl>C1COCC1.O>[CH:1]1([N:4]([CH3:22])[C:5]2[C:6]3[C:17]4[CH2:18][CH2:19][CH2:20][CH2:21][C:16]=4[S:15][C:7]=3[N:8]=[C:9]([CH2:11][C:12]([N:35]([CH3:36])[CH3:34])=[O:13])[N:10]=2)[CH2:2][CH2:3]1

Participants

6

Reactant 3

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 897136992-(4-(Cyclopropyl(methyl)amino)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-2-yl)acetic acid

Product 1

HCID 716547422-(4-(cyclopropyl(methyl)amino)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-2-yl)-N,N-dimethylacetamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To 2-(4-(cyclopropyl(methyl)amino)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-2-yl)acetic acid (100 mg, 0.000315 mol) in anhydrous THF (10 ml) 2M dimethyl amine in THF (0.017 g, 0.000378 mol) and HOBt (0.051 g, 0.000378 mol) were added. This mixture was cooled to 0° C. and then treated with EDC HCl (0.120 g, 0.00063 mol). The reaction mixture was allowed to warm to room temperature and kept stirred for 16 h. After completion, the reaction was diluted with water (50 ml) and extracted with ethyl acetate (25 ml×3). Combined organic extracts were washed with water (50 ml), dried over anhydrous Na2SO4 and concentrated under vacuum to get crude compound. It was then purified by column chromatography by using 100-200 mesh silica gel. Pure compound was eluted in 1-2% MeOH: DCM to afford 2-(4-(cyclopropyl(methyl)amino)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-2-yl)-N,N-dimethylacetamide as a pale yellow oil. Yield—50 mg, (46.29%); 1H-NMR: (400 MHz, CDCl3); δ=3.97 (s, 2H), 3.04 (s, 3H), 3.01 (s, 3H), 2.97 (s, 3H), 2.89-2.80 (m, 5H), 1.92-1.86 (m, 2H), 1.77-1.71 (m, 2H), 0.72-0.67 (m, 2H), 0.45-0.41 (m, 2H); LC-MS [M+H]=345.3; HPLC purity=98.78%.

Workup

  1. temperatureto warm to room temperature
  2. extractionextracted with ethyl acetate (25 ml×3)
  3. washCombined organic extracts were washed with water (50 ml)
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated under vacuum
  6. customto get crude compound
  7. customIt was then purified by column chromatography
  8. washPure compound was eluted in 1-2% MeOH

Sources & evidence

ORD record
ord-aa30e37b37e34fc0b940980b65b78962
Source dataset
uspto-grants-2016_07
Patent number
US09399647B2

Reaction notes

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