Sodium borohydride → HCID 90067518, compound

HRID 929210Notes

Reaction equation

HRID 929210 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[NH:22][C:21]([O:23][C@@H:24]3[CH2:28][O:27][C@@H:26]4[C@:29]([CH2:33][CH:34]=[O:35])([OH:32])[CH2:30][O:31][C@H:25]34)=[N:20][C:5]2=[N:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:10][CH:9]=1.[BH4-].[Na+]>CO>[Cl:1][C:2]1[CH:3]=[C:4]2[NH:22][C:21]([O:23][C@@H:24]3[CH2:28][O:27][C@@H:26]4[C@:29]([CH2:33][CH2:34][OH:35])([OH:32])[CH2:30][O:31][C@H:25]34)=[N:20][C:5]2=[N:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)=[CH:10][CH:9]=1

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 90042613HCID 90042613, compound

Product 1

HCID 90067518HCID 90067518, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

A stirred suspension of 2-[(3R,3aR,6R,6aS)-3-[[6-chloro-5-(4-phenylphenyl)-1H-imidazo[4,5-b]pyridin-2-yl]oxy]-6-hydroxy-3,3a,5,6a-tetrahydro-2H-furo[3,2-b]furan-6-yl]acetaldehyde (12.9 mg, 0.026 mmol) in methanol (0.5 ml) was cooled to 0° C. in an ice bath. Sodium boro-hydride (3.5 mg, 0.093 mmol) was added to the reaction mixture, resulting in gas evolution. The reaction mixture was allowed to warm to room temperature overnight. The next day, the reaction mixture was directly purified by preparative HPLC reverse phase (C-18), using a 30×150 mm Sunfire™ column and eluting with a 20%-100% acetonitrile/water+0.05% TFA gradient followed by a 100% acetonitrile+0.05% TFA flush. The product fractions were combined, evaporated under reduced pressure, and lyophilized from ethanol and benzene to give the title compound as a white solid. LC-MS: calculated for C26H24ClN3O5 493.14 observed m/e: 494.24 (M+H)+ (Rt 1.17/2 min); 1H NMR δ (ppm) (CD3OD): 7.97 (s, 1H), 7.74-7.77 (m, 4H), 7.71 (d, J=7.7 Hz, 2H), 7.48 (t, J=7.6 Hz, 2H), 7.38 (t, J=7.4 Hz, 1H), 5.58 (qt, J=5.3 Hz, J=10.6 Hz, 1H), 4.98 (t, J=5.3 Hz, 1H), 4.29 (d, J=4.9 Hz, 1H), 4.15-4.20 (m, 2H), 3.77-3.84 (m, 2H), 3.71 (abqt, J=8.7 Hz, J=21.2 Hz, 2H), 1.85 (t, J=6.6 Hz, 2H).

Workup

  1. customresulting in gas evolution
  2. temperatureto warm to room temperature overnight
  3. customThe next day, the reaction mixture was directly purified by preparative HPLC reverse phase (C-18)
  4. washeluting with a 20%-100% acetonitrile/water+0.05% TFA
  5. customflush
  6. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-2ad0f362258f47589186a2f68b94eef1
Source dataset
uspto-grants-2016_03
Patent number
US09290517B2

Reaction notes

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