Dimethylformamide → HCID 89761590, compound

HRID 528590Notes

Reaction equation

HRID 528590 reaction equation
Br[C:2]1[CH:7]=[C:6]([CH:8]([CH3:10])[CH3:9])[CH:5]=[CH:4][C:3]=1[N:11]1[CH2:16][CH2:15][O:14][C:13]2[CH:17]=[C:18]([S:21]([N:24](CC3C=CC(OC)=CC=3)[C:25]3[S:26][CH:27]=[CH:28][N:29]=3)(=[O:23])=[O:22])[CH:19]=[CH:20][C:12]1=2.[CH3:39][N:40](C=O)C>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[C-]#N.[Zn+2].[C-]#N>[C:39]([C:2]1[CH:7]=[C:6]([CH:8]([CH3:10])[CH3:9])[CH:5]=[CH:4][C:3]=1[N:11]1[CH2:16][CH2:15][O:14][C:13]2[CH:17]=[C:18]([S:21]([NH:24][C:25]3[S:26][CH:27]=[CH:28][N:29]=3)(=[O:23])=[O:22])[CH:19]=[CH:20][C:12]1=2)#[N:40]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 89761414HCID 89761414, compound

Product 1

HCID 89761590HCID 89761590, compound

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Procedure

A reaction vial was charged with 4-(2-bromo-4-isopropylphenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (0.175 g, 0.285 mmol), Pd(PPh3)4 (0.049 g, 0.043 mmol), and zinc cyanide (0.050 g, 0.427 mmol), and DMF (1.139 ml) was added. The reaction was sealed and heated to 100° C. overnight until complete conversion to the desired product. The reaction was diluted with ethyl acetate and filtered over a membrane, washing with ethyl acetate. The filtrate was then washed with small amounts of water (×4) to remove residual DMF. The organics were dried over sodium sulfate, filtered and concentrated in vacuo to yield a crude yellow oil. The oil was dissolved in methanol and was loaded onto a 2-g SCX column (product eluted with methanol wash). After concentration, the crude product was diluted with DCM (2.0 mL) and TFA (1.0 mL) was added and the reaction was stirred at RT for 30 minutes until complete deprotection. The reaction was then concentrated in vacuo, and was purified by silica gel chromatography eluting with 0-100% ethyl acetate in heptanes to yield 4-(2-cyano-4-isopropylphenyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (0.055 g, 0.125 mmol, 43.8% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.23 (d, J=6.94 Hz, 6 H) 2.93-3.05 (m, 1 H) 3.72-3.77 (m, 2 H) 4.30-4.36 (m, 2 H) 6.42 (d, J=8.41 Hz, 1 H) 6.79 (d, J=4.60 Hz, 1 H) 7.13-7.17 (m, 1 H) 7.18 (d, J=2.15 Hz, 1 H) 7.22 (d, J=4.60 Hz, 1 H) 7.49 (d, J=8.41 Hz, 1 H) 7.68 (dd, J=8.46, 2.20 Hz, 1 H) 7.83 (d, J=2.15 Hz, 1 H) 12.58 (br. s., 1 H). m/z (ESI) 441.3 (M+H)+.

Workup

  1. customA reaction
  2. additionwas added
  3. customThe reaction was sealed

Sources & evidence

ORD record
ord-50d02f30b8d74dc5b0a4e16aff518e2c
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

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