Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → HCID 57695053, compound

HRID 1644184Notes

Reaction equation

HRID 1644184 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH:25]1([C:31]2[C:32]3[CH:33]=[CH:34][C:35]([C:54](=[O:62])[NH:55][S:56]([CH:59]([CH3:61])[CH3:60])(=[O:58])=[O:57])=[CH:36][C:37]=3[N:38]3[CH2:44][C:43]([C:45](O)=[O:46])=[CH:42][C:41]4[CH:48]=[C:49]([O:52][CH3:53])[CH:50]=[CH:51][C:40]=4[C:39]=23)[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1.[CH3:63][N:64]1[CH2:73][CH2:72][C:67]2([NH:71][CH2:70][CH2:69][CH2:68]2)[CH2:66][CH2:65]1>CN(C=O)C.CO>[CH:25]1([C:31]2[C:32]3[CH:33]=[CH:34][C:35]([C:54]([NH:55][S:56]([CH:59]([CH3:61])[CH3:60])(=[O:57])=[O:58])=[O:62])=[CH:36][C:37]=3[N:38]3[CH2:44][C:43]([C:45]([N:71]4[C:67]5([CH2:66][CH2:65][N:64]([CH3:63])[CH2:73][CH2:72]5)[CH2:68][CH2:69][CH2:70]4)=[O:46])=[CH:42][C:41]4[CH:48]=[C:49]([O:52][CH3:53])[CH:50]=[CH:51][C:40]=4[C:39]=23)[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30]1

Participants

6

Reactant 3

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 576950541,8-Diazaspiro[4.5]decane, 8-Methyl-HCID 6677313813-cyclohexyl-10-((isopropylsulfonyl)carbamoyl)-3-methoxy-7H-indolo[2,1-a][2]benzazepine-6-carboxylic acid

Product 1

HCID 57695053HCID 57695053, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

HATU (30 mg, 0.079 mmol) was added to a stirring solution of 13-cyclohexyl-10-((isopropylsulfonyl)carbamoyl)-3-methoxy-7H-indolo[2,1-a][2]benzazepine-6-carboxylic acid (34 mg, 0.063 mmol) and 8-methyl-1,8-diazaspiro[4.5]decane (24 mg, 0.16 mmol) in DMF (0.5 mL) and TEA (100 μL, 0.72 mmol) and the reaction mixture was stirred at rt for 1 h (complete by LCMS). The reaction mixture was diluted with MeOH, filtered and purified by preparative HPLC (CH3CN/H2O w/10 mM NH4OAc) to yield 13-cyclohexyl-N-(isopropylsulfonyl)-3-methoxy-6-((8-methyl-1,8-diazaspiro[4.5]dec-1-yl)carbonyl)-7H-indolo[2,1-a][2]benzazepine-10-carboxamide (19.7 mg, 0.029 mmol, 46% yield) as a yellow solid. 1HNMR (300 MHz, CD3OD) δ ppm 1.10-2.20 (m, 22H), 2.76 (s, 3H), 2.67-3.49 (m, 9H), 3.91 (s, 3H), 3.86-4.00 (m, 1H), 4.27-4.45 (m, 1H), 5.07-5.20 (m, 1H), 6.91 (s, 1H), 7.03 (d, J=2.6 Hz, 1H), 7.13 (dd, J=8.8, 2.6 Hz, 1H), 7.56 (d, J=8.8 Hz, 1H), 7.73 (dd, J=8.4, 1.5 Hz, 1H), 7.81 (d, J=8.4 Hz, 1H), 8.26 (br s, 1H). LC-MS retention time: 2.64 min; m/z 671 (MH−). LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna 10u C18 4.6×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 5 mL/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 4 min, a hold time of 1 min, and an analysis time of 5 min where solvent A was 5% acetonitrile/95% H2O/10 mM ammonium acetate and solvent B was 5% H2O/95% acetonitrile/10 mM ammonium acetate. MS data was determined using a Micromass Platform for LC in electrospray mode.

Workup

  1. filtrationfiltered
  2. custompurified by preparative HPLC (CH3CN/H2O w/10 mM NH4OAc)

Sources & evidence

ORD record
ord-3d9b33431f7b48abbea2e3581961ac69
Source dataset
uspto-grants-2012_02
Patent number
US08124601B2

Reaction notes

Loading…