Sodium Acetate → 8-Azetidin-1-ylmethyl-2-(1H-indol-4-yl)-4-morpholin-4-yl-pyrido[3',2':4,5]furo[3,2-d]pyrimidine

HRID 1499030Notes

Reaction equation

HRID 1499030 reaction equation
[CH:1]1([N:4]([CH2:6][C:7]2[CH:34]=[N:33][C:10]3[O:11][C:12]4[C:17]([N:18]5[CH2:23][CH2:22][O:21][CH2:20][CH2:19]5)=[N:16][C:15]([C:24]5[CH:32]=[CH:31][CH:30]=[C:29]6[C:25]=5[CH:26]=[CH:27][NH:28]6)=[N:14][C:13]=4[C:9]=3[CH:8]=2)[CH3:5])C[CH2:2]1.Cl.N1CCC1.CC([O-])=O.[Na+].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[BH3-]C#N.[Na+]>[Cl-].[Na+].O.CCOC(C)=O.CO.C(Cl)Cl.CN(C=O)C>[N:4]1([CH2:6][C:7]2[CH:34]=[N:33][C:10]3[O:11][C:12]4[C:17]([N:18]5[CH2:23][CH2:22][O:21][CH2:20][CH2:19]5)=[N:16][C:15]([C:24]5[CH:32]=[CH:31][CH:30]=[C:29]6[C:25]=5[CH:26]=[CH:27][NH:28]6)=[N:14][C:13]=4[C:9]=3[CH:8]=2)[CH2:1][CH2:2][CH2:5]1

Participants

11

Reactant 5

HCID 517045Sodium AcetateHCID 5003444Sodium cyanoborohydrideHCID 5049666Sodium triacetoxyborohydrideHCID 12308726Azetidine hydrochlorideHCID 50991103Cyclopropyl-[2-(1H-indol-4-yl)-4-morpholin-4-yl-pyrido[3',2':4,5]furo[3,2-d]pyrimidin-8-ylmethyl]-methyl-amine

Product 1

HCID 509911058-Azetidin-1-ylmethyl-2-(1H-indol-4-yl)-4-morpholin-4-yl-pyrido[3',2':4,5]furo[3,2-d]pyrimidine

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To compound 23 (as per Example S above) (17 mg, 0.04 mmol) in a mixture of dry DMF (2 mL), CH2Cl2 (0.5 mL) and MeOH (0.2 mL) was added azetidine hydrochloride (16 mg, 0.17 mmol) and NaOAc (14 mg, 0.17 mnnol) under Ar(g). After 5 minutes NaBH(OAc)3 (27 m0, 0.13 mmol) and NaBH3CN (5.4 mg, 0.09 mmol) were added and the reaction mixture was stirred for 16 h. EtOAc (45 mL) was added along with 50% saturated brine (5 mL); the layers were separated, extracted with EtOAc (3×10 mL), dried (MgSO4) and concentrated in vacuo. Purification by flash column chromatography on silica (eluant 2-8% MeOH/CH2Cl2) furnished U (5.4 mg, 0.012 mmol, 28%) as an off-white solid.

Workup

  1. customthe layers were separated
  2. extractionextracted with EtOAc (3×10 mL)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customPurification by flash column chromatography on silica (eluant 2-8% MeOH/CH2Cl2)
  6. customfurnished U (5.4 mg, 0.012 mmol, 28%) as an off-white solid

Sources & evidence

ORD record
ord-ff5c10c798a147e895b5bcb2961fee96
Source dataset
uspto-grants-2015_12
Patent number
US09200007B2

Reaction notes

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