Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate → N-[(3-aminooxetan-3-yl)methyl]-6-methyl-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)thieno[3,2-d]pyrimidin-4-amine

HRID 1910454Notes

Reaction equation

HRID 1910454 reaction equation
[O:1]=[S:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[CH2:6][N:5]([C:13]2[NH:14][C:15](=O)[C:16]3[S:21][C:20]([CH3:22])=[CH:19][C:17]=3[N:18]=2)[CH2:4][CH2:3]1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.N1(C2CCCCCCCCCC2)CCCN=CCCCCC1.[NH2:73][CH2:74][C:75]1([NH2:79])[CH2:78][O:77][CH2:76]1>CN(C)C=O.O>[NH2:79][C:75]1([CH2:74][NH:73][C:15]2[C:16]3[S:21][C:20]([CH3:22])=[CH:19][C:17]=3[N:18]=[C:13]([N:5]3[CH2:6][C:7]4[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=4[S:2](=[O:1])[CH2:3][CH2:4]3)[N:14]=2)[CH2:78][O:77][CH2:76]1

Participants

7

Reactant 4

HCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 217130163-(Aminomethyl)oxetan-3-amineHCID 1296629601,8-Diazabicycloundec-7eneHCID 1363597882-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylthieno[3,2-d]pyrimidin-4(3H)-one

Product 1

HCID 71548784N-[(3-aminooxetan-3-yl)methyl]-6-methyl-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)thieno[3,2-d]pyrimidin-4-amine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

A suspension of 2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylthieno[3,2-d]pyrimidin-4(3H)-one (250 mg, 0.72 mmol), benzotriazol-1-yloxy-tris(dimethylamino)-phosphonium hexafluorophosphate (415 mg, 0.94 mmol) and 1,8-diazabicycloundec-7-ene (165 mg, 1.08 mmol) in anhydrous N,N-dimethylformamide (10 mL) was stirred at r.t. for 10 min, then a solution of 3-aminomethyl-oxetan-3-ylamine (150 mg, 1.44 mmol) in N,N-dimethylformamide (5 mL) was added dropwise. After the addition was complete, the mixture was heated at 60° C. overnight, then it was diluted with water (50 mL), extracted by dichloromethane, washed by brine, dried with anhydrous sodium sulfate. The solvent was removed and the residue was purified by preparative HPLC to afford N-[(3-aminooxetan-3-yl)methyl]-6-methyl-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)thieno[3,2-d]pyrimidin-4-amine as a white solid. MS obsd. (ESI+) [(M+H)+] 430, 1H NMR (400 MHz, METHANOL-d4) δ ppm 7.67-7.80 (m, 2H), 7.45 (t, J=5.8 Hz, 2H), 6.82 (s, 1H), 5.21 (d, J=15.4 Hz, 1H), 4.71 (br. s., 1H), 4.63 (d, J=6.3 Hz, 2H), 4.46-4.56 (m, 2H), 4.01 (s, 2H), 3.30-3.49 (m, 4H), 2.55 (s, 3H).

Workup

  1. additionAfter the addition
  2. temperaturethe mixture was heated at 60° C. overnight
  3. extractionextracted by dichloromethane
  4. washwashed by brine
  5. dry with materialdried with anhydrous sodium sulfate
  6. customThe solvent was removed
  7. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-85ac215028b34677a3d7c5ffe1b920f0
Source dataset
uspto-grants-2013_12
Patent number
US08604019B2

Reaction notes

Loading…