Triethylamine → 9-(1-Isopropyl-1H-pyrazol-5-yl)-6,7-dihydroimidazo[1,2-d]pyrido[3,2-b][1,4]oxazepine-3-carboxamide

HRID 1629147Notes

Reaction equation

HRID 1629147 reaction equation
[CH:1]([N:4]1[C:8]([C:9]2[N:10]=[C:11]3[CH2:17][CH2:16][O:15][C:14]4[CH:18]=[C:19]([C:22]([OH:24])=O)[CH:20]=[N:21][C:13]=4[N:12]3[CH:25]=2)=[CH:7][CH:6]=[N:5]1)([CH3:3])[CH3:2].C[N:27](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>CN(C=O)C>[CH:1]([N:4]1[C:8]([C:9]2[N:10]=[C:11]3[CH2:17][CH2:16][O:15][C:14]4[CH:18]=[C:19]([C:22]([NH2:27])=[O:24])[CH:20]=[N:21][C:13]=4[N:12]3[CH:25]=2)=[CH:7][CH:6]=[N:5]1)([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 582043789-(1-Isopropyl-1H-pyrazol-5-yl)-6,7-dihydroimidazo[1,2-d]pyrido[3,2-b][1,4]oxazepine-3-carboxylic acid

Product 1

HCID 582049309-(1-Isopropyl-1H-pyrazol-5-yl)-6,7-dihydroimidazo[1,2-d]pyrido[3,2-b][1,4]oxazepine-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 17 mg (0.05 mmol) of 9-(1-isopropyl-1H-pyrazol-5-yl)-6,7-dihydroimidazo[1,2-d]pyrido[3,2-b][1,4]oxazepine-3-carboxylic acid, 30 mg, (0.061 mmol) of HATU and 0.022 ml (0.155 mmol) of triethylamine in 2 ml of DMF was stirred for 10 min. Ammonia (gas) was bubbled through the mixture for 5 min. The mixture was stirred for 1 hour, concentrated in vacuum and partitioned between ethyl acetate and 0.01 N aqueous HCl. The organic layer was concentrated and the residue purified on 4 g silica column eluting with 7-8% Methanol in DCM to give 114. Yield 2.4 mg. MS(ESI+) 339.2. 1H NMR (400 MHz, CH3OH+D2O) δ 8.70 (d, J=1.8, 1H), 8.33 (s, 1H), 8.05 (d, J=1.8, 1H), 7.52 (s, 1H), 6.48 (d, J=1.6, 1H), 5.16 (dd, J=13.2, 6.6, 1H), 4.56 (t, J=5.1, 2H), 3.52-3.45 (m, 2H), 1.49 (d, J=6.6, 6H).

Workup

  1. customAmmonia (gas) was bubbled through the mixture for 5 min
  2. stirringThe mixture was stirred for 1 hour
  3. concentrationconcentrated in vacuum
  4. custompartitioned between ethyl acetate and 0.01 N aqueous HCl
  5. concentrationThe organic layer was concentrated
  6. customthe residue purified on 4 g silica column
  7. washeluting with 7-8% Methanol in DCM

Sources & evidence

ORD record
ord-50d8a0c701084fd4947449bdb2319f2f
Source dataset
uspto-grants-2014_07
Patent number
US08785626B2

Reaction notes

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