Water → HCID 89761891, compound

HRID 528543Notes

Reaction equation

HRID 528543 reaction equation
[NH:1]1[CH2:6][CH:5]=[C:4]([C:7]2[CH:12]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:10]=[CH:9][C:8]=2[N:17]2[CH2:22][CH2:21][O:20][C:19]3[CH:23]=[C:24]([S:27]([NH:30][C:31]4[S:32][CH:33]=[CH:34][N:35]=4)(=[O:29])=[O:28])[CH:25]=[CH:26][C:18]2=3)[CH2:3][CH2:2]1.O.[C:37](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>CCOC(C)=O>[CH3:37][N:1]1[CH2:2][CH:3]=[C:4]([C:7]2[CH:12]=[C:11]([C:13]([F:14])([F:16])[F:15])[CH:10]=[CH:9][C:8]=2[N:17]2[CH2:22][CH2:21][O:20][C:19]3[CH:23]=[C:24]([S:27]([NH:30][C:31]4[S:32][CH:33]=[CH:34][N:35]=4)(=[O:28])=[O:29])[CH:25]=[CH:26][C:18]2=3)[CH2:5][CH2:6]1

Participants

6

Reactant 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 71711173HCID 71711173, compound

Product 1

HCID 89761891HCID 89761891, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

EXAMPLE 44 was prepared by charging a 10-mL round bottomed flask with 4-(2-(1,2,3,6-tetrahydropyridin-4-yl)-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide, (EXAMPLE 38, 0.040 g, 0.077 mmol). The reaction vessel was then flushed with N2 gas and the solid starting materials were dissolved in methanol (0.4 mL). To the resulting solution, formaldehyde 37% wt in water (0.085 mL, 1.148 mmol) was added and the mixture was stirred for 5 min at room temperature. Sodium triacetoxyborohydride (0.243 g, 1.148 mmol) was added portion wise and the resulting solution was stirred for 10 min. The reaction mixture was poured into a sep. funnel containing sat. NaHCO3 and EtOAc. The aqueous layer was washed with EtOAc (3×25 mL), the organic layers were combined and dried over Na2SO4. The organic layer was filtered and concentrated to give pure 4-(2-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (0.030 g, 0.056 mmol) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.18 (d, J=5.58 Hz, 3 H) 2.41 (br. s., 2 H) 2.91 (br. s., 2 H) 3.57 (br. s., 3 H) 4.25 (br. s., 2 H) 5.22 (s, 1 H) 5.80 (br. s., 1 H) 6.40 (t, J=8.61 Hz, 1 H) 6.60 (d, J=3.62 Hz, 1 H) 6.85 (d, J=4.70 Hz, 1 H) 7.03-7.12 (m, 1 H) 7.13-7.22 (m, 1 H) 7.35 (d, J=4.50 Hz, 1 H) 7.46-7.63 (m, 2 H) 7.64-7.78 (m, 1 H).

Workup

  1. customEXAMPLE 44 was prepared
  2. customThe reaction vessel was then flushed with N2 gas
  3. dissolutionthe solid starting materials were dissolved in methanol (0.4 mL)
  4. additionwas added
  5. stirringthe resulting solution was stirred for 10 min
  6. additionThe reaction mixture was poured into a sep
  7. washThe aqueous layer was washed with EtOAc (3×25 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationThe organic layer was filtered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-fdf058f2c8ef46cfbceffbefeac85cf9
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

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