Dimethylformamide → HCID 131733231, compound

HRID 508709Notes

Reaction equation

HRID 508709 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:14]3[CH:15]=[CH:16][C:17](B4[O:23][C:22](C)(C)[C:21](C)(C)[O:20]4)=[CH:18][C:13]=3[CH2:12][N:11]([CH3:28])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.Br[C:30]1[CH:38]=[CH:37][C:33]([C:34]([NH2:36])=[O:35])=[CH:32][CH:31]=1.[C:39](=[O:42])([O-:41])[O-].[Cs+].[Cs+].CN([CH:48]=[O:49])C>O.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe]>[C:39]([C@@H:21]([C@H:22]([C:48]([OH:49])=[O:35])[OH:23])[OH:20])([OH:41])=[O:42].[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:14]3[CH:15]=[CH:16][C:17]([C:30]4[CH:38]=[CH:37][C:33]([C:34]([NH2:36])=[O:35])=[CH:32][CH:31]=4)=[CH:18][C:13]=3[CH2:12][N:11]([CH3:28])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 696834-BromobenzamideHCID 68555637HCID 68555637, compound

Product 1

HCID 131733231HCID 131733231, compoundYield 10%

Reagents, catalysts & solvents 2

HCID 53485975CID 53485975CatalystHCID 962WaterSolvent

Procedure

Following a procedure similar to the one in Example 36, 1-(4-chlorophenyl)-4-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepine (100 mg, 0.251 mmol), 4-bromobenzamide (60 mg, 0.301 mmol), cesium carbonate (245 mg, 0.752 mmol) and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (20 mg, 0.0251 mmol) in DMF (2.0 mL) and water (0.5 mL) gave the desired product (10.0 mg, 10%) as a colorless oil. To a solution of the benzodiazepine (10.0 mg, 0.025 mmol) in methanol (1 mL) and water (3 mL) was added L-tartaric acid (4.0 mg, 0.025 mmol) and the resultant solution was lyophilized overnight to give 4-(1-(4-chlorophenyl)-4-methyl-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-7-yl)benzamide, L-tartrate salt (13.6 mg, 97%, AUC HPLC>99%) as a yellow solid: 1H NMR (CD3OD, 500 MHz) δ 7.97 (d, J=8.4 Hz, 2H), 7.87 (s, 1H), 7.78-7.75 (m, 3H), 7.28 (d, J=8.3 Hz, 1H), 7.22 (d, J=9.0 Hz, 2H), 6.89 (d, J=9.0 Hz, 2H), 4.43 (s, 1.3H), 4.27 (s, 2H), 3.98 (bs, 2H), 3.35-3.33 (m, 2H), 2.86 (s, 3H); ESI MS m/z 392 [M+H]+.

Sources & evidence

ORD record
ord-c5b3bd552591472699f5212764bb37af
Source dataset
uspto-grants-2015_08
Patent number
US09096546B2

Reaction notes

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