(S)-2-Methylpyrrolidine-2-carboxamide → (25)-1-(2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydroimidazo[1,2-d]pyrido[3,4-f][1,4]oxazepin-9-yl)-2-methylpyrrolidine-2-carboxamide

HRID 1629442Notes

Reaction equation

HRID 1629442 reaction equation
[CH:1]([N:4]1[C:8]([C:9]2[N:18]=[C:17]3[N:11]([CH2:12][CH2:13][O:14][C:15]4[CH:22]=[C:21](O)[N:20]=[CH:19][C:16]=43)[CH:10]=2)=[N:7][C:6](C)=[N:5]1)([CH3:3])[CH3:2].[CH3:25][C@@:26]1([C:31]([NH2:33])=[O:32])[CH2:30][CH2:29][CH2:28][NH:27]1>>[CH:1]([N:4]1[C:8]([C:9]2[N:18]=[C:17]3[C:16]4[CH:19]=[N:20][C:21]([N:27]5[CH2:28][CH2:29][CH2:30][C@@:26]5([CH3:25])[C:31]([NH2:33])=[O:32])=[CH:22][C:15]=4[O:14][CH2:13][CH2:12][N:11]3[CH:10]=2)=[N:7][CH:6]=[N:5]1)([CH3:3])[CH3:2]

Participants

3

Reactant 2

HCID 14829625(S)-2-Methylpyrrolidine-2-carboxamideHCID 178432612HCID 178432612, compound

Product 1

HCID 58204456(25)-1-(2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydroimidazo[1,2-d]pyrido[3,4-f][1,4]oxazepin-9-yl)-2-methylpyrrolidine-2-carboxamide

Procedure

Following the procedures for Examples 339 and 408, 2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a,9-triaza-benzo[e]azulen-8-ol and (S)-2-methyl-pyrollidine-2-carboxylic acid amide were reacted. The crude product was passed down a Isolute SCX-2 column, eluting with methanol then 2M NH3 in methanol. The basic fractions were concentrated in vacuo and the resultant residue subjected to reverse phase HPLC (C18 column, gradient 15 to 75% Methanol in water+0.1% HCO2H). The appropriate fractions were evaporated to dryness, passed down an Isolute NH2 column, eluting with methanol then further triturated in diethyl ether to give 402 as a white solid. LCMS: RT=2.79 min, [M+H]+=423. 1H NMR 400 MHz (CD3OD) δ: 9.14 (1 H, s), 7.93 (1 H, s), 7.69 (1 H, s), 6.05 (1 H, s), 5.99 (1 H, m), 4.51-4.50 (4 H, m), 3.70 (1 H, m), 3.57 (1 H, m), 3.50 (1 H, m), 2.36-2.33 (1 H, m), 2.10-2.08 (2 H, m), 1.63 (3 H, s), 1.56 (6 H, dd, J=6.63, 2.34 Hz)

Workup

  1. customwere reacted
  2. washeluting with methanol
  3. concentrationThe basic fractions were concentrated in vacuo
  4. customThe appropriate fractions were evaporated to dryness
  5. washeluting with methanol
  6. customthen further triturated in diethyl ether

Sources & evidence

ORD record
ord-16b5d9ca6d7346caad41e3f4b4cae7aa
Source dataset
uspto-grants-2014_07
Patent number
US08785626B2

Reaction notes

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