Sodium triacetoxyborohydride → HCID 89498080, compound

HRID 1430307Notes

Reaction equation

HRID 1430307 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C:11]([C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:22]=1[CH2:21][N:20]([C:23]1[N:28]=[C:27]([C:29]([O:31]C(C)(C)C)=[O:30])[C:26]([C:36]3[CH:37]=[N:38][N:39]([CH2:42][C:43]4([O:49][CH2:50][CH:51]=O)[CH2:48][CH2:47][CH2:46][CH2:45][CH2:44]4)[C:40]=3[CH3:41])=[CH:25][CH:24]=1)[CH2:19][CH2:18]2)=[O:12].[NH:53]1[CH2:58][CH2:57][S:56](=[O:60])(=[O:59])[CH2:55][CH2:54]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.C(OCC)(=O)C.C(O)(C(F)(F)F)=O>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C:11]([C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:22]=1[CH2:21][N:20]([C:23]1[N:28]=[C:27]([C:29]([OH:31])=[O:30])[C:26]([C:36]3[CH:37]=[N:38][N:39]([CH2:42][C:43]4([O:49][CH2:50][CH2:51][N:53]5[CH2:58][CH2:57][S:56](=[O:60])(=[O:59])[CH2:55][CH2:54]5)[CH2:44][CH2:45][CH2:46][CH2:47][CH2:48]4)[C:40]=3[CH3:41])=[CH:25][CH:24]=1)[CH2:19][CH2:18]2)=[O:12]

Participants

7

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 6484228Thiomorpholine 1,1-dioxideHCID 89498148HCID 89498148, compound

Product 1

HCID 89498080HCID 89498080, compound

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolvent2×HCID 6422Trifluoroacetic acidSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of EXAMPLE 167F (72 mg) and thiomorpholine 1,1-dioxide (13.5 mg) in dichloromethane (3 mL) was added sodium triacetoxyborohydride (32 mg). The mixture was stirred overnight. The mixture was dissolved in ethyl acetate (200 mL) and washed with 2N aqueous NaOH and brine, and dried over Na2SO4. Filtration and evaporation of the solvent gave crude product which was dissolved in dichloromethane (2 mL) and TFA (2 mL). After stirring overnight, the solvent was evaporated. The residue was purified by reverse phase chromatography using a Gilson system, eluting with 20-80% acetonitrile in 0.1% TFA water solution to provide the title compound. 1H NMR (300 MHz, dimethylsulfoxide-d6). δ ppm 12.86 (s, 1H), 8.04 (d, 1H), 7.79 (d, 1H), 7.62 (d, 1H), 7.42 (m, 5H), 6.97 (d, 1H), 4.96 (s, 2H), 4.10 (s, 3H), 3.53 (m, 8H), 3.02 (t, 2H), 2.13 (s, 3H), 1.43 (m, 10H).

Workup

  1. washwashed with 2N aqueous NaOH and brine
  2. dry with materialdried over Na2SO4
  3. filtrationFiltration and evaporation of the solvent
  4. customgave crude product which
  5. stirringAfter stirring overnight
  6. customthe solvent was evaporated
  7. customThe residue was purified by reverse phase chromatography
  8. washeluting with 20-80% acetonitrile in 0.1% TFA water solution

Sources & evidence

ORD record
ord-9f69e1b34443464885e3e4fe86e994c9
Source dataset
uspto-grants-2015_01
Patent number
US08940737B2

Reaction notes

Loading…