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

HRID 1499029Notes

Reaction equation

HRID 1499029 reaction equation
C1([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])CC1.[BH3-]C#N.[Na+].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].CC([O-])=O.[Na+].Cl.[CH:59]1([CH2:62]NC)[CH2:61][CH2:60]1>CN(C=O)C.CO.C(Cl)Cl>[CH:59]1([CH2:62][N:4]([CH2:6][C:7]2[CH:34]=[N:33][C:10]3[O:11][C:12]4[C:17]([N:18]5[CH2:19][CH2:20][O:21][CH2:22][CH2:23]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])[CH2:61][CH2:60]1

Participants

9

Reactant 5

HCID 517045Sodium AcetateHCID 5003444Sodium cyanoborohydrideHCID 5049666Sodium triacetoxyborohydrideHCID 12919210(Cyclopropylmethyl)(methyl)amine 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 50991104Cyclopropylmethyl-[2-(1H-indol-4-yl)-4-morpholin-4-yl-pyrido[3',2':4,5]furo[3,2-d]pyrimidin-8-ylmethyl]-methyl-amine

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of compound 23 (as per Example S above) (19 mg, 0.048 mmol, leg), NaBH3CN (6.0 mg, 0.096 mmol. 2 eq), NaBH(OAc)3 (31 mg, 0.144 mmol, 3 eq), NaOAc (15.7 mg, 0.19 mmol, 4 eq) in a mixture of anhydrous CH2Cl2 (2 mL), MeOH (2 mL) and DMF (0.5 mL) was added cyclopropylmethyl-methyl-amine hydrochloride (23 mg, 0.19 mmol, 4 eq) under Ar(g). The reaction mixture was stirred at rt overnight. Solvents were removed in vacuo. Then, the residue was partitioned with H2O (10 mL) and extracted with CH2Cl2 (3×10 mL) and EtOAc (2×10 mL). The combined organic extracts were dried over MgSO4 and the solvent was removed in vacuo. The residue was further purified by silica gel column chromatography with CH2Cl2/MeOH (1:0-47:3) to yield the product, T, as a white solid (8.35 mg, 37%).

Workup

  1. customSolvents were removed in vacuo
  2. customThen, the residue was partitioned with H2O (10 mL)
  3. extractionextracted with CH2Cl2 (3×10 mL) and EtOAc (2×10 mL)
  4. dry with materialThe combined organic extracts were dried over MgSO4
  5. customthe solvent was removed in vacuo
  6. customThe residue was further purified by silica gel column chromatography with CH2Cl2/MeOH (1:0-47:3)
  7. customto yield the product, T

Sources & evidence

ORD record
ord-994d382b50ae4f1282b3211768e3fb70
Source dataset
uspto-grants-2015_12
Patent number
US09200007B2

Reaction notes

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