HCID 11350559, compound → HCID 59857422, compound

HRID 555423Notes

Reaction equation

HRID 555423 reaction equation
[C:1]([C:5]1[CH:31]=[CH:30][CH:29]=[CH:28][C:6]=1[O:7][C:8]1[C:13]([NH:14][C:15]2[NH:16][C:17]3[CH:23]=[C:22]([C:24](OC)=[O:25])[CH:21]=[CH:20][C:18]=3[N:19]=2)=[CH:12][CH:11]=[CH:10][N:9]=1)([CH3:4])([CH3:3])[CH3:2].[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[C:1]([C:5]1[CH:31]=[CH:30][CH:29]=[CH:28][C:6]=1[O:7][C:8]1[C:13]([NH:14][C:15]2[NH:16][C:17]3[CH:23]=[C:22]([CH2:24][OH:25])[CH:21]=[CH:20][C:18]=3[N:19]=2)=[CH:12][CH:11]=[CH:10][N:9]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 11350559HCID 11350559, compoundHCID 21226445Aluminium lithium hydride

Product 1

HCID 59857422HCID 59857422, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of methyl 2-(2-(2-tert-butylphenoxy)pyridin-3-ylamino)-3H-benzo[d]imidazole-5-carboxylate (Example 14, 65 mg, 0.156 mmol), in dry THF (6 mL) was added to a cooled (0° C.) solution of LiAlH4 in THF (0.39 mL, 1.0 M solution). After 2 h, the reaction was allowed to warm to rt and stirred for 24 h. The mixture was cooled to 0° C., the excess of LiAlH4 was destroyed very with a saturated solution of NH4Cl. The product was extracted with EtOAc (4×20 mL), dried over MgSO4 and evaporated to yield a white solid. Example 145 was obtained after preparative HPLC purification (continuous gradient from 10% B to 60% B; A=90:10:0.1 H2O:MeOH:TFA; B=90:10:0.1 MeOH:H2O:TFA). tR=4.589 min (Shimadzu Phenomenex S5 ODS 4.6×50 mm Luna 4.6×50 mm; flow rate 2.5 mL/inn; detection at 220 nM; Gradient elution 0% to 100% B over 8 min; (A=10% MeOH, 90% H2O, 0.2% H3PO4 & B=90% MeOH, 10% H2O, 0.2% H3PO4). HRMS (ESI) m/z calcd for C23H25N4O2 [M+H]+ 389.1978. found 389.1972.

Workup

  1. temperatureThe mixture was cooled to 0° C.
  2. customthe excess of LiAlH4 was destroyed very with a saturated solution of NH4Cl
  3. extractionThe product was extracted with EtOAc (4×20 mL)
  4. dry with materialdried over MgSO4
  5. customevaporated
  6. customto yield a white solid
  7. customExample 145 was obtained
  8. customafter preparative HPLC purification (continuous gradient from 10% B to 60% B
  9. washGradient elution 0% to 100% B over 8 min

Sources & evidence

ORD record
ord-41356f1ea2b04f1eba382bb7813e3a17
Source dataset
uspto-grants-2011_11
Patent number
US08053450B2

Reaction notes

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