Sodium borohydride → HCID 90067516, compound

HRID 929208Notes

Reaction equation

HRID 929208 reaction equation
[BH4-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]2[NH:24][C:23]([O:25][C@@H:26]3[CH2:30][O:29][C@@H:28]4[C@@:31]([OH:36])([CH:34]=[O:35])[CH2:32][O:33][C@H:27]34)=[N:22][C:7]2=[N:8][C:9]=1[C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:12][CH:11]=1>CO>[Cl:3][C:4]1[CH:5]=[C:6]2[NH:24][C:23]([O:25][C@@H:26]3[CH2:30][O:29][C@@H:28]4[C@:31]([CH2:34][OH:35])([OH:36])[CH2:32][O:33][C@H:27]34)=[N:22][C:7]2=[N:8][C:9]=1[C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)=[CH:12][CH:11]=1

Participants

4

Reactant 2

HCID 4311764Sodium borohydride4×HCID 90041879HCID 90041879, compound

Product 1

HCID 90067516HCID 90067516, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

Sodium borohydride (1.3 mg, 0.034 mmol) was added to a stirred solution of (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-carbaldehyde (5.4 mg, 0.011 mmol) in methanol (0.5 ml) that had been cooled to 0° C. in an ice bath. After 1.5 hours, additional sodium borohydride (3.0 mg, 0.079 mmol) was added to the reaction mixture. After an additional 1.5 hours, additional sodium borohydride (2.8 mg, 0.074 mmol) was added to the reaction mixture. After another hour, the reaction mixture was placed in the refrigerator overnight. In the morning, the reaction mixture was removed from the refrigerator and placed in an ice bath. Additional sodium borohydride (3.2 mg, 0.085 mmol) was added to the reaction mixture. After 1.5 hours, the reaction mixture was removed from the ice bath and allowed to warm to room temperature. 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%-80% acetonitrile/water+0.05% TFA gradient followed by a 80% acetonitrile/water+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 C25H22ClN3O5 479.12 observed m/e: 480.18 (M+H)+ (Rt 1.16/2 min); 1H NMR δ (ppm) (CD3OD): 7.86 (s, 1H), 7.73-7.77 (m, 4H), 7.71 (d, J=7.8 Hz, 2H), 7.48 (t, J=7.6 Hz, 2H), 7.38 (t, J=6.8 Hz, 1H), 5.56 (qt, J=5.4 Hz, 1H), 4.98 (t, J=5.3 Hz, 1H), 4.30 (d, J=5.0 Hz, 1H), 4.20 (dd, J=5.6 Hz, J=10.3 Hz, 1H), 4.15 (dd, J=5.1 Hz, J=10.0 Hz, 1H), 3.80 (d, J=8.7 Hz, 1H), 3.67 (d, J=8.8 Hz, 1H), 3.52-3.58 (m, 2H).

Workup

  1. waitAfter an additional 1.5 hours
  2. waitAfter another hour
  3. customwas placed in the refrigerator overnight
  4. customIn the morning, the reaction mixture was removed from the refrigerator
  5. customplaced in an ice bath
  6. waitAfter 1.5 hours
  7. customthe reaction mixture was removed from the ice bath
  8. temperatureto warm to room temperature
  9. customThe reaction mixture was directly purified by preparative HPLC reverse phase (C-18)
  10. washeluting with a 20%-80% acetonitrile/water+0.05% TFA
  11. customflush
  12. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-ce74f5a46b3b4d569c4245d265fc91c0
Source dataset
uspto-grants-2016_03
Patent number
US09290517B2

Reaction notes

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