Triethylamine → HCID 67076240, compound

HRID 1676545Notes

Reaction equation

HRID 1676545 reaction equation
[CH:1]1([N:5]2[CH2:11][C:10]([F:13])([F:12])[C:9](=[O:14])[N:8]([CH3:15])[C:7]3[CH:16]=[N:17][C:18]([NH:20][C:21]4[CH:29]=[CH:28][C:24]([C:25](O)=[O:26])=[CH:23][C:22]=4[O:30][CH3:31])=[N:19][C:6]2=3)[CH2:4][CH2:3][CH2:2]1.C(N(CC)CC)C.CN(C(=[N+](C)C)ON1C2=NC=CC=C2N=N1)C.F[P-](F)(F)(F)(F)F.Cl.[CH:64]1[C:76]2[CH:75]([CH2:77][O:78][C:79](=[O:87])[NH:80][CH:81]3[CH2:86][CH2:85][NH:84][CH2:83][CH2:82]3)[C:74]3[C:69](=[CH:70][CH:71]=[CH:72][CH:73]=3)[C:68]=2[CH:67]=[CH:66][CH:65]=1>C(OCC)(=O)C.CN(C)C=O>[CH:64]1[C:76]2[CH:75]([CH2:77][O:78][C:79](=[O:87])[NH:80][CH:81]3[CH2:82][CH2:83][N:84]([C:25](=[O:26])[C:24]4[CH:28]=[CH:29][C:21]([NH:20][C:18]5[N:17]=[CH:16][C:7]6[N:8]([CH3:15])[C:9](=[O:14])[C:10]([F:12])([F:13])[CH2:11][N:5]([CH:1]7[CH2:4][CH2:3][CH2:2]7)[C:6]=6[N:19]=5)=[C:22]([O:30][CH3:31])[CH:23]=4)[CH2:85][CH2:86]3)[C:74]3[C:69](=[CH:70][CH:71]=[CH:72][CH:73]=3)[C:68]=2[CH:67]=[CH:66][CH:65]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 9886HexafluorophosphateHCID 27562184-(Fmoc-amino)piperidine hydrochlorideHCID 4641409(Dimethylamino)-N,N-dimethyl(3H-(1,2,3)triazolo(4,5-b)pyridin-3-yloxy)methaniminiumHCID 580150754-(9-cyclobutyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoic acid

Product 1

HCID 67076240HCID 67076240, compoundYield 61.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 0.200 g (0.46 mmole) of 4-(9-cyclobutyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoic acid (I-1), 0.186 g (1.84 mmole) of triethylamine, 0.220 g (0.51 mmole) of N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-methanaminium, hexafluorophosphate(1-) (1:1) and 5 mL of dimethylformamide was stirred for 15 minutes and then 0.182 g (0.51 mmole) of 4-piperidinyl-carbamic acid 9H-fluoren-9-ylmethyl ester monohydrochloride was added. The mixture was stirred for 3 hours, then taken up in 100 mL of ethyl acetate and washed twice with 100 mL of water and then 100 mL of brine. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with hexane-ethyl acetate (gradient 50:50-0:100) to give 0.210 g of {1-[4-(9-Cyclobutyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoyl]-piperidin-4-yl}-carbamic acid 9H-fluoren-9-ylmethyl ester.

Workup

  1. stirringThe mixture was stirred for 3 hours
  2. washwashed twice with 100 mL of water
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel chromatography
  7. washeluting with hexane-ethyl acetate (gradient 50:50-0:100)

Sources & evidence

ORD record
ord-6b02421117dc48c798372df943e16c89
Source dataset
uspto-grants-2011_08
Patent number
US08003785B2

Reaction notes

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