[3-(Aminomethyl)oxetan-3-yl]methanamine → HCID 86691436, compound

HRID 540295Notes

Reaction equation

HRID 540295 reaction equation
C(O[C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([CH2:19][OH:20])[CH:17]=2)[N:12]=[C:11]([N:21]2[CH2:27][C:26]3[CH:28]=[CH:29][CH:30]=[CH:31][C:25]=3[S:24](=[O:32])[CH2:23][CH2:22]2)[N:10]=1)C1C=CC=CC=1.C(OC1C2C(=CC=C(CO)C=2)N=C(N2CC3C=CC=CC=3S(=O)(=O)CC2)N=1)C1C=CC=CC=1.[O:66]1[CH2:69][C:68]([CH2:72][NH2:73])([CH2:70][NH2:71])[CH2:67]1>O>[NH2:71][CH2:70][C:68]1([CH2:72][NH:73][C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([CH2:19][OH:20])[CH:17]=3)[N:12]=[C:11]([N:21]3[CH2:27][C:26]4[CH:28]=[CH:29][CH:30]=[CH:31][C:25]=4[S:24](=[O:32])[CH2:23][CH2:22]3)[N:10]=2)[CH2:69][O:66][CH2:67]1

Participants

5

Reactant 3

HCID 10953471[3-(Aminomethyl)oxetan-3-yl]methanamineHCID 71255298HCID 71255298, compoundHCID 71262273HCID 71262273, compound

Product 1

HCID 86691436HCID 86691436, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
160 °C

Procedure

A mixture of [4-(benzyloxy)-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinazolin-6-yl]methanol and [4-(benzyloxy)-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinazolin-6-yl]methanol (700 mg, about 1.57 mmol) and oxetane-3,3-diyldimethanamine (700 mg, 6.03 mmol) was heated at 160° C. for 30 minutes. After being cooled to room temperature, the reaction mixture was diluted with water (10 mL), extracted with dichloromethane (20 mL×3). The organic layers were washed with brine (40 mL), dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by preparative HPLC to afford [4-({[3-(aminomethyl)oxetan-3-yl]methyl}amino)-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinazolin-6-yl]methanol, MS obsd. (ESI+) [(M+H)+] 454, 1H NMR (400 MHz, DMSO-d6) δ ppm 8.139 (s, 1 H), 7.918 (s, 1 H), 7.71 (m, 2 H), 7.48 (m, 3 H), 7.316 (d, J=8 Hz, 1 H), 5.21 (m, 2 H), 4.75 (m, 2 H), 4.51 (m, 4 H), 4.369 (s, 3 H), 3.93 (brs, 1 H), 3.15 (brs, 2 H), 2.989 (s, 2 H), and [4-({[3-(aminomethyl)oxetan-3-yl]methyl}amino)-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinazolin-6-yl]methanol, MS obsd. (ESI+) [(M+H)+] 470, 1H NMR (400 MHz, DMSO-d6) δ ppm 8.197 (s, 1 H), 7.789 (m, 3 H), 7.62 (t, J=7.2 Hz, 1 H), 7.48 (m, 2 H), 7.316 (s, 1 H), 5.12 (m, 3 H), 4.48 (m, 8 H), 3.917 (s, 2 H), 3.569 (brs, 2 H), 2.951 (brs, 2 H).

Workup

  1. temperatureAfter being cooled to room temperature
  2. extractionextracted with dichloromethane (20 mL×3)
  3. washThe organic layers were washed with brine (40 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-2fdfc464ccb84fb7abcb6bc45976d791
Source dataset
uspto-grants-2014_10
Patent number
US08871756B2

Reaction notes

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