Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → 1-oxo-N-[3-(trifluoromethyl)-1,2-oxazol-5-yl]-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indole-8-carboxamide

HRID 1748347Notes

Reaction equation

HRID 1748347 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[O:25]=[C:26]1[C:32]2=[CH:33][C:34]3[CH:35]=[CH:36][C:37]([C:40]([OH:42])=O)=[CH:38][C:39]=3[N:31]2[CH2:30][CH2:29][CH2:28][NH:27]1.C(N=P1N(C)CCCN1C)(C)(C)C.[F:56][C:57]([F:65])([F:64])[C:58]1[CH:62]=[C:61]([NH2:63])[O:60][N:59]=1>ClC(Cl)C>[O:25]=[C:26]1[C:32]2=[CH:33][C:34]3[CH:35]=[CH:36][C:37]([C:40]([NH:63][C:61]4[O:60][N:59]=[C:58]([C:57]([F:65])([F:64])[F:56])[CH:62]=4)=[O:42])=[CH:38][C:39]=3[N:31]2[CH2:30][CH2:29][CH2:28][NH:27]1

Participants

6

Reactant 4

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 139139963-(Trifluoromethyl)-1,2-oxazol-5-amineHCID 672357061-oxo-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indole-8-carboxylic acid2×HCID 178480484HCID 178480484, compound

Product 1

HCID 683233941-oxo-N-[3-(trifluoromethyl)-1,2-oxazol-5-yl]-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indole-8-carboxamideYield 15.5%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of HATU (0.086 g, 0.225 mmol) and 1-oxo-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indole-8-carboxylic acid (Intermediate J, 0.050 g, 0.205 mmol) in dichlorethane (1 mL) in a microwave vial is heated in a microwave reactor at 60° C. for 60 minutes. Polystyrene bound 2-tert-butylimino-1,3-dimethylperhydro-1,3,2-diazaphosphorine (0.307 g, 0.615 mmol) and 3-trifluoromethyl-isoxazol-5-ylamine (0.094 g, 0.615 mmol) are added to the mixture and the vial is heated in a microwave at 120° C. for an additional 60 minutes. The resin is filtered off and washed several times with DMF. After the removal of solvent, the residue is purified by flash column chromatography using 5% methanol/dichlorormethane to afford title compound (0.012 g, 15.5%) as a white solid.

Workup

  1. additionare added to the mixture
  2. temperaturethe vial is heated in a microwave at 120° C. for an additional 60 minutes
  3. filtrationThe resin is filtered off
  4. washwashed several times with DMF
  5. customAfter the removal of solvent
  6. customthe residue is purified by flash column chromatography

Sources & evidence

ORD record
ord-cb794ca266b340dfae756487b04fe00f
Source dataset
uspto-grants-2015_10
Patent number
US09150577B2

Reaction notes

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