Acetone → 2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-9-(5-(1-isopropylpiperidin-3-yl)-1-methyl-1H-pyrazol-4-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

HRID 1530681Notes

Reaction equation

HRID 1530681 reaction equation
[CH3:1][C:2]1[N:6]=[C:5]([C:7]2[N:8]=[C:9]3[N:19]([CH:20]=2)[CH2:18][CH2:17][O:16][C:15]2[C:10]3=[CH:11][CH:12]=[C:13]([C:21]3[CH:22]=[N:23][N:24]([CH3:32])[C:25]=3[CH:26]3[CH2:31][CH2:30][CH2:29][NH:28][CH2:27]3)[CH:14]=2)[N:4]([CH:33]([CH3:35])[CH3:34])[N:3]=1.[CH3:36][C:37]([CH3:39])=O.[BH3-]C#N.[Na+]>C(O)C>[CH:33]([N:4]1[C:5]([C:7]2[N:8]=[C:9]3[C:10]4[CH:11]=[CH:12][C:13]([C:21]5[CH:22]=[N:23][N:24]([CH3:32])[C:25]=5[CH:26]5[CH2:31][CH2:30][CH2:29][N:28]([CH:37]([CH3:39])[CH3:36])[CH2:27]5)=[CH:14][C:15]=4[O:16][CH2:17][CH2:18][N:19]3[CH:20]=2)=[N:6][C:2]([CH3:1])=[N:3]1)([CH3:35])[CH3:34]

Participants

5

Reactant 3

HCID 180AcetoneHCID 5003444Sodium cyanoborohydrideHCID 683127572-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-9-(1-methyl-5-(piperidin-3-yl)-1H-pyrazol-4-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

Product 1

HCID 683129352-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-9-(5-(1-isopropylpiperidin-3-yl)-1-methyl-1H-pyrazol-4-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepineYield 29.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
20 °C

Procedure

To a solution of 4-[3-methyl-1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-12-[1-methyl-5-(piperidin-3-yl)-1H-pyrazol-4-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca1(14), 2,4,10,12-pentaene (140 mg, 0.300 mmol) and acetone (174 mg, 3.0 mmol) in ethanol (10 mL) was added Ti(Oi-Pr)4 (171 mg, 0.60 mmol). After being stirred at 20° C. for 20 min, NaBH3CN (37 mg, 0.60 mmol) was added and stirred at 20° C. for 24 h. The solvent was removed and several drops of water were added. The solid was filtered off and the filtrate was evaporated to afford the crude product, which was purified prep-HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/1% formic acid, 17 min) to give racemic 268 (45 mg, 29% yield). LCMS (ESI): RT=5.41 min, m/z: 515.3 [M+H+]. 1H NMR (500 MHz, DMSO-d6) δ 8.40 (d, J=8.0 Hz, 1H), 7.91 (s, 1H), 7.43 (s, 1H), 7.09 (dd, J=8.5, 1.5 Hz, 1H), 6.94 (s, 1H), 5.90-5.82 (m, 1H), 4.53 (s, 4H), 3.90 (s, 3H), 3.11 (m, 1H), 3.10-2.66 (m, 3H), 2.50 (t, J=2.0 Hz, 1H), 2.26 (s, 3H), 2.08 (m, 1H), 1.80-1.20 (m, 10H), 0.95-0.92 (m, 6H)

Workup

  1. stirringstirred at 20° C. for 24 h
  2. customThe solvent was removed
  3. additionseveral drops of water were added
  4. filtrationThe solid was filtered off
  5. customthe filtrate was evaporated
  6. customto afford the crude product, which
  7. customwas purified prep-HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/1% formic acid, 17 min)

Sources & evidence

ORD record
ord-a00e7a35e9344a27a27f0c67496a1e3b
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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