Trimethyl orthoformate → HCID 67045291, compound

HRID 2203873Notes

Reaction equation

HRID 2203873 reaction equation
[Si:1]([O:8][CH2:9][CH:10]=O)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].Cl.[NH2:13][C@@H:14]1[CH2:19][CH2:18][CH2:17][N:16]([C:20]2[C:25]([Br:26])=[CH:24][N:23]=[C:22]3[NH:27][CH:28]=[C:29]([NH:30][C:31](=[O:40])[C:32]4[CH:37]=[CH:36][C:35]([F:38])=[C:34]([Cl:39])[CH:33]=4)[C:21]=23)[CH2:15]1.CCN(C(C)C)C(C)C.C(OC)(OC)OC.[BH4-].[Na+].C([O-])(O)=O.[Na+]>CO.C(Cl)Cl>[Br:26][C:25]1[C:20]([N:16]2[CH2:17][CH2:18][CH2:19][C@@H:14]([NH:13][CH2:10][CH2:9][O:8][Si:1]([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:2])[CH3:3])[CH2:15]2)=[C:21]2[C:29]([NH:30][C:31](=[O:40])[C:32]3[CH:37]=[CH:36][C:35]([F:38])=[C:34]([Cl:39])[CH:33]=3)=[CH:28][NH:27][C:22]2=[N:23][CH:24]=1

Participants

9

Reactant 6

HCID 9005Trimethyl orthoformateHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 41877882-((Tert-butyldimethylsilyl)oxy)acetaldehydeHCID 4311764Sodium borohydrideHCID 67045092HCID 67045092, compound

Product 1

HCID 67045291HCID 67045291, compoundYield 39.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

2-(tert-Butyldimethylsilyloxy)acetaldehyde (0.037 mL, 0.19 mmol) was added to a mixture of (R)—N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-chloro-4-fluorobenzamide (70 mg, 0.13 mmol, Example 62), DIEA (0.068 mL, 0.39 mmol), and trimethyl orthoformate (280 mg, 2.6 mmol) in MeOH (3 mL), and the reaction was stirred at room temperature for 18 hours. NaBH4 (9.8 mg, 0.26 mmol) was then added, and the reaction was stirred for 1 hour. The mixture was poured into a saturated solution of NaHCO3, and extracted with CH2Cl2. The combined organic fractions were dried (MgSO4), filtered, and concentrated in vacuo. The residue obtained was purified by column chromatography on silica gel eluting with 2% MeOH:CH2Cl2 to provide (R)—N-(5-bromo-4-(3-(2-(tert-butyldimethylsilyloxy)ethylamino)piperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-chloro-4-fluorobenzamide (32 mg, 39% yield).

Workup

  1. stirringthe reaction was stirred for 1 hour
  2. extractionextracted with CH2Cl2
  3. dry with materialThe combined organic fractions were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue obtained
  7. customwas purified by column chromatography on silica gel eluting with 2% MeOH

Sources & evidence

ORD record
ord-30580a234fce44a8aa645a7abe5f507a
Source dataset
uspto-grants-2016_06
Patent number
US09365568B2

Reaction notes

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