Sodium borohydride → HCID 59605452, compound

HRID 1923381Notes

Reaction equation

HRID 1923381 reaction equation
C([O:3][C:4](=O)[C:5]([N:8]1[CH2:11][C:10]([C:13]2[N:14]([CH3:39])[C:15]3[C:20]([N:21]=2)=[C:19]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[N:18]=[C:17]([N:28]2[C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=4[N:30]=[C:29]2[CH2:37][CH3:38])[N:16]=3)([F:12])[CH2:9]1)([CH3:7])[CH3:6])C.[BH4-].[Na+]>>[CH2:37]([C:29]1[N:28]([C:17]2[N:16]=[C:15]3[C:20]([N:21]=[C:13]([C:10]4([F:12])[CH2:9][N:8]([C:5]([CH3:7])([CH3:6])[CH2:4][OH:3])[CH2:11]4)[N:14]3[CH3:39])=[C:19]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)[N:18]=2)[C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=2[N:30]=1)[CH3:38]

Participants

3

Reactant 2

HCID 4311764Sodium borohydride2×HCID 67492927HCID 67492927, compound

Product 1

HCID 59605452HCID 59605452, compoundYield 56.2%

Procedure

To a solution of 2-{3-[2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]-3-fluoroazetidin-1-yl}-2-methylpropionic acid ethyl ester (40 mg, 0.07 mmol) in IMS (4 mL) was added NaBH4 (28 mg, 0.73 mmol) and the resulting mixture stirred at r.t for 3 h. Further NaBH4 (28 mg, 0.73 mmol) was added and the mixture stirred for a further 18 h. The reaction mixture was quenched with H2O, extracted with EtOAc and the organic phase dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, MeOH:EtOAc, 0-10%) then dissolved in a mixture of MeCN and H2O and allowed to freeze-dry affording 850 as a white solid (20 mg, 54%). LCMS (method I): RT 2.64 min, [M+H]+ 509.4. 1H NMR (DMSO, 400 MHz): δ 8.05-8.04 (1 H, m), 7.64-7.63 (1 H, m), 7.26-7.25 (2 H, m), 4.58-4.49 (1 H, m), 4.44-4.14 (4 H, brd m), 4.08 (2 H, dd, J=18.70, 9.19 Hz), 3.81-3.74 (9 H, m), 3.28-3.26 (2 H, m), 3.19 (2 H, d, J=5.40 Hz), 1.34 (3 H, t, J=7.43 Hz), 0.91 (6 H, s)

Workup

  1. stirringthe mixture stirred for a further 18 h
  2. customThe reaction mixture was quenched with H2O
  3. extractionextracted with EtOAc
  4. dry with materialthe organic phase dried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by column chromatography (Si-PCC, MeOH:EtOAc, 0-10%)
  7. dissolutionthen dissolved in a mixture of MeCN and H2O
  8. customto freeze-dry

Sources & evidence

ORD record
ord-c3d769ff613f45bfbd40c15d1b0e82b3
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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