Water → HCID 89762621, compound

HRID 528587Notes

Reaction equation

HRID 528587 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][O:11][C:10]3[CH:14]=[C:15]([S:18]([N:21](CC4C=CC(OC)=CC=4)[C:22]4[S:23][CH:24]=[CH:25][N:26]=4)(=[O:20])=[O:19])[CH:16]=[CH:17][C:9]2=3)=[C:4]([C:36]#[N:37])[CH:3]=1.[F:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=1B(O)O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O>O1CCOCC1.C(Cl)Cl.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[C:36]([C:4]1[CH:3]=[C:2]([C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][C:39]=2[F:38])[CH:7]=[CH:6][C:5]=1[N:8]1[CH2:13][CH2:12][O:11][C:10]2[CH:14]=[C:15]([S:18]([NH:21][C:22]3[S:23][CH:24]=[CH:25][N:26]=3)(=[O:19])=[O:20])[CH:16]=[CH:17][C:9]1=2)#[N:37]

Participants

8

Reactant 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 27343542-Fluorophenylboronic acidHCID 897618304-(4-bromo-2-cyanophenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide

Product 1

HCID 89762621HCID 89762621, compoundYield 80%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of PdCl2(dppf)-CH2Cl2 adduct (0.017 g, 0.021 mmol), 4-(4-bromo-2-cyanophenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (0.124 g, 0.208 mmol), (2-fluorophenyl)boronic acid (0.032 g, 0.228 mmol, Aldrich) and potassium phosphate (0.220 g, 1.038 mmol) in dioxane (0.553 ml)/water (0.277 ml) was heated to 90° C. for 1 h until completion. The reaction was cooled to RT and then diluted with DCM and washed with water. The organics were dried via phase separator (Radleys Discovery Technologies) and concentrated in vacuo. The material was taken up in a mixture of DCM and methanol, and further purified using a 2-g SCX column (product eluted with methanol wash). After concentration, DCM (1.0 mL) and TFA (0.5 mL) were added and stirred at RT for 3 h until complete deprotection. The reaction was concentrated in vacuo and purified via silica-gel chromatography, eluting with 0-100% ethyl acetate in heptanes to yield, after concentration, 4-(3-cyano-2′-fluoro-[1,1′-biphenyl]-4-yl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (0.082 g, 0.166 mmol, 80% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.79-3.86 (m, 2 H) 4.32-4.40 (m, 2 H) 6.64 (d, J=8.51 Hz, 1 H) 6.80 (d, J=4.50 Hz, 1 H) 7.17-7.21 (m, 1 H) 7.21-7.24 (m, 2 H) 7.31-7.40 (m, 2 H) 7.45-7.53 (m, 1 H) 7.60-7.68 (m, 2 H) 7.95 (dt, J=8.56, 1.83 Hz, 1 H) 8.11 (s, 1 H) 12.62 (br. S., 1 H). m/z (ESI) 493.0 (M+H)+.

Workup

  1. washwashed with water
  2. customThe organics were dried via phase separator (Radleys Discovery Technologies)
  3. concentrationconcentrated in vacuo
  4. additionThe material was taken up in a mixture of DCM and methanol
  5. customfurther purified
  6. washa 2-g SCX column (product eluted with methanol wash)
  7. concentrationAfter concentration, DCM (1.0 mL) and TFA (0.5 mL)
  8. additionwere added
  9. concentrationThe reaction was concentrated in vacuo
  10. custompurified via silica-gel chromatography
  11. washeluting with 0-100% ethyl acetate in heptanes
  12. customto yield

Sources & evidence

ORD record
ord-99e9a0b6306d4974ade2cb8a27092f8d
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

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