4-Methylmorpholine → 1-oxo-N-(5-phenyl-1,2-oxazol-3-yl)-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indole-8-carboxamide

HRID 1748348Notes

Reaction equation

HRID 1748348 reaction equation
[O:1]=[C:2]1[C:8]2=[CH:9][C:10]3[CH:11]=[CH:12][C:13]([C:16]([OH:18])=O)=[CH:14][C:15]=3[N:7]2[CH2:6][CH2:5][CH2:4][NH:3]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:43]1([C:49]2[O:53][N:52]=[C:51]([NH2:54])[CH:50]=2)[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1.CN1CCOCC1>CN1C(=O)CCC1>[O:1]=[C:2]1[C:8]2=[CH:9][C:10]3[CH:11]=[CH:12][C:13]([C:16]([NH:54][C:51]4[CH:50]=[C:49]([C:43]5[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=5)[O:53][N:52]=4)=[O:18])=[CH:14][C:15]=3[N:7]2[CH2:6][CH2:5][CH2:4][NH:3]1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 36207925-Phenyl-1,2-oxazol-3-amineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 672357061-oxo-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indole-8-carboxylic acid2×

Product 1

HCID 683234141-oxo-N-(5-phenyl-1,2-oxazol-3-yl)-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indole-8-carboxamideYield 5.2%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A 2-5 mL microwave reactor vial is charged with a solution of 1-oxo-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indole-8-carboxylic acid (Intermediate J, 25 mg, 0.10 mmol) in NMP (2 mL). HATU (47 mg, 0.12 mmol) is added and the mixture is stirred at room temperature for 30 min. 5-phenyl-3-aminoisoxazole (66 mg, 0.41 mmol) and N-methylmorpholine (41 mg, 0.41 mmol) are added and the vial is sealed with a Teflon lined septa cap and is irradiated in a microwave reactor at 100° C. for 30 min then at 150° C. for 90 min. The mixture is purified via preparative HPLC using a gradient elution from 10-90% acetonitrile/water with 0.1% TFA to obtain the title compound (2 mg, 5%). LCMS: 387.20 (M+H+). (System V1)

Workup

  1. customsepta cap
  2. customis irradiated in a microwave reactor at 100° C. for 30 min
  3. waitat 150° C. for 90 min
  4. customThe mixture is purified via preparative HPLC
  5. washa gradient elution from 10-90% acetonitrile/water with 0.1% TFA

Sources & evidence

ORD record
ord-848c866d73c8498fa9bf2cc745766698
Source dataset
uspto-grants-2015_10
Patent number
US09150577B2

Reaction notes

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