Sodium cyanoborohydride → HCID 21874294, compound

HRID 723456Notes

Reaction equation

HRID 723456 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:15]3=[C:16]([CH2:19][C:20]4([OH:27])[CH2:25][CH2:24][C:23](=O)[CH2:22][CH2:21]4)[CH:17]=[CH:18][N:14]3[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8].[BH3-]C#[N:30].[Na+]>CO>[NH2:30][CH:23]1[CH2:24][CH2:25][C:20]([CH2:19][C:16]2[CH:17]=[CH:18][N:14]3[C:15]=2[C:10]([NH:9][C:4]2[CH:5]=[CH:6][C:7]([F:8])=[C:2]([Cl:1])[CH:3]=2)=[N:11][CH:12]=[N:13]3)([OH:27])[CH2:21][CH2:22]1

Participants

4

Reactant 2

HCID 5003444Sodium cyanoborohydrideHCID 21874252HCID 21874252, compound

Product 1

HCID 21874294HCID 21874294, compoundYield 15%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 4-[4-(3-chloro-4-fluoro-phenylamino)-pyrrolo[2,1-f][1,2,4]triazin-5-ylmethyl]-4-hydroxy-cyclohexanone (24 mg, 0.06 mmole) in dry MeOH (0.5 mL) was added powdered 3A molecular sieves (24 mg), (10 eq) NH4OAc (48 mg, 0.06 mmole), and NaCNBH3 (4 mg, 0.06 mmole); the reaction stirred under nitrogen for 12 hr. The reaction mixture was filtered and a 15% NaOH solution was added. After 10 min, the mixture was diluted with DCM (50 mL) and washed with water. The organic phase was dried (Na2SO4) and the solvent was removed. The material was purified and separated by preparative HPLC to afford the title compound (3.5 mg, 15%) and the cis isomer (7.9 mg, 32%). The title compound: MS: 390 (M+H)+; HPLC Ret Time: 2.070 min (XTERRA 4.6×50 mm S5 column, 3 min gradient, 4 mL/min). The cis isomer: MS: 390 (M+H)+; HPLC Ret Time: 2.190 min (XTERRA 4.6×50 mm S5 column, 3 min gradient, 4 mL/min).

Workup

  1. filtrationThe reaction mixture was filtered
  2. additiona 15% NaOH solution was added
  3. waitAfter 10 min
  4. additionthe mixture was diluted with DCM (50 mL)
  5. washwashed with water
  6. dry with materialThe organic phase was dried (Na2SO4)
  7. customthe solvent was removed
  8. customThe material was purified
  9. customseparated by preparative HPLC

Sources & evidence

ORD record
ord-c5eb5eed674749ea87eab0f7dee48134
Source dataset
uspto-grants-2006_11
Patent number
US07141571B2

Reaction notes

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