3-Tolylboronic acid → (4As)-10-(2-fluorophenyl)-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,5]benzodiazepin-6(7h)-one

HRID 80516Notes

Reaction equation

HRID 80516 reaction equation
FC1C=CC=CC=1B(O)O.CC1C=C(B(O)O)C=CC=1.[CH2:21]([N:28]1[CH2:50][CH2:49][N:31]2[C:32]3[CH:41]=[C:40]([C:42]4[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=4[F:48])[CH:39]=[CH:38][C:33]=3[NH:34][C:35](=[O:37])[CH2:36][C@H:30]2[CH2:29]1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>C(O)C>[CH2:21]([N:28]1[CH2:50][CH2:49][N:31]2[C:32]3[CH:41]=[C:40]([C:42]4[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=4[F:48])[CH:39]=[CH:38][C:33]=3[NH:34][C:35](=[O:37])[CH2:36][C@H:30]2[CH2:29]1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.[F:48][C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][C:42]=1[C:40]1[CH:39]=[CH:38][C:33]2[NH:34][C:35](=[O:37])[CH2:36][C@H:30]3[CH2:29][NH:28][CH2:50][CH2:49][N:31]3[C:32]=2[CH:41]=1

Participants

6

Reactant 3

HCID 27339503-Tolylboronic acidHCID 27343542-Fluorophenylboronic acidHCID 67250222HCID 67250222, compound

Product 2

HCID 67250037(4As)-10-(2-fluorophenyl)-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,5]benzodiazepin-6(7h)-oneHCID 67250222HCID 67250222, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

(4aS)-3-Benzyl-10-(2-fluorophenyl)-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,5]benzodiazepin-6(7H)-one was prepared according to the procedure outlined in Example 89 substituting 2-fluorophenylboronic acid for 3-methylphenylboronic acid and Example 116B for Example 4. The intermediate (4aS)-3-benzyl-10-(2-fluorophenyl)-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,5]benzodiazepin-6(7H)-one was purified via HPLC, and underwent benzyl removal in ethanol (20 mL) with Pd(OH)2—C (20%, 1 wet, 76 mg, 1.250 mmol) which was stirred for 2 hours under H2 (30 psi) at room temperature. The catalyst was removed by filtration. HPLC purification afforded the title compound. as the trifluoroacetic acid salt. 1H NMR (500 MHz, DMSO-d6) δ ppm 7.50-7.56 (m, 1H), 7.36-7.43 (m, 1H), 7.20-7.30 (m, 4H), 7.07 (d, J=8.24 Hz, 1H), 3.57-3.63 (m, 1H), 3.31-3.40 (m, 4H), 2.95-3.07 (m, 2H), 2.70 (dd, J=13.58, 7.17 Hz, 1H), 2.07 (d, J=12.51 Hz, 1H); MS (DCI+) m/z 312 (M+H)+.

Workup

  1. customThe catalyst was removed by filtration
  2. customHPLC purification

Sources & evidence

ORD record
ord-7a803c330f2547e3b8266bc51efdd1d4
Source dataset
uspto-grants-2014_09
Patent number
US08846663B2

Reaction notes

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