(2S,4R)-4-methoxy-pyrrolidine-2-carboxylic acid amide → (2S,4R)-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)-4-methoxypyrrolidine-2-carboxamide

HRID 886414Notes

Reaction equation

HRID 886414 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][O:26][C@H:27]1[CH2:31][NH:30][C@H:29]([C:32]([NH2:34])=[O:33])[CH2:28]1>O>[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:30]5[CH2:31][C@H:27]([O:26][CH3:25])[CH2:28][C@H:29]5[C:32]([NH2:34])=[O:33])=[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

4

Reactant 2

HCID 67050845(2S,4R)-4-methoxy-pyrrolidine-2-carboxylic acid amideHCID 178432612HCID 178432612, compound

Product 1

HCID 58204938(2S,4R)-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)-4-methoxypyrrolidine-2-carboxamideYield 32%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Following the procedure 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 (2S,4R)-4-methoxy-pyrrolidine-2-carboxylic acid amide were reacted. The reaction mixture was diluted with water passed down an SCX-2 cartridge, washed with DCM, ethyl acetate and methanol and products eluted with 2M ammonia in methanol. Appropriate fractions were concentrated in vacuo and the resultant residue was triturated in diethyl ether and methanol, filtered and dried to give 407 as beige solid (45 mg, 32%). LCMS: RT=2.60 min, [M+H]+=439. 1H NMR 400 MHz (CDCl3) δ: 9.27 (1H, s), 7.83 (1H, s), 7.57 (1H, s), 6.79 (1H, br, s), 6.00 (1H, s), 5.98 (1H, m), 5.29 (1H, br, s), 4.65 (1H, dd, J=8.28, 4.87 Hz), 4.49-4.47 (2H, m), 4.39-4.34 (2H, m), 4.23 (1H, t, J=5.53 Hz), 3.74 (1H, dd, J=10.34, 5.70 Hz), 3.51-3.46 (1H, m), 3.36 (3H, s), 2.52-2.51 (1H, m), 2.24-2.23 (1H, m), 1.55-1.54 (6H, m)

Workup

  1. customwere reacted
  2. washwashed with DCM, ethyl acetate and methanol and products
  3. washeluted with 2M ammonia in methanol
  4. concentrationAppropriate fractions were concentrated in vacuo
  5. customthe resultant residue was triturated in diethyl ether
  6. filtrationmethanol, filtered
  7. customdried

Sources & evidence

ORD record
ord-d1960c05b20c4733a8ff137475d82436
Source dataset
uspto-grants-2012_08
Patent number
US08242104B2

Reaction notes

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