Diisopropylethylamine → HCID 67496450, compound

HRID 1628332Notes

Reaction equation

HRID 1628332 reaction equation
[NH2:1][C@@H:2]([CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:3]([N:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([C:14]3[CH:15]=[N:16][CH:17]=[N:18][CH:19]=3)[CH:12]=2)[CH2:7][CH2:6]1)=[O:4].[S:27]1[CH:31]=[C:30]([CH:32]=O)[N:29]=[CH:28]1.C(N(C(C)C)CC)(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([BH3-])#N.[Na+]>ClCCCl.C1COCC1.ClCCl.C(=O)(O)[O-].[Na+]>[C:21]1([CH2:20][C@H:2]([NH:1][CH2:32][C:30]2[N:29]=[CH:28][S:27][CH:31]=2)[C:3]([N:5]2[C:13]3[C:8](=[CH:9][CH:10]=[C:11]([C:14]4[CH:19]=[N:18][CH:17]=[N:16][CH:15]=4)[CH:12]=3)[CH2:7][CH2:6]2)=[O:4])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 2763214Thiazole-4-carboxaldehydeHCID 5003444Sodium cyanoborohydrideHCID 5049666Sodium triacetoxyborohydrideHCID 67496036HCID 67496036, compound

Product 1

HCID 67496450HCID 67496450, compoundYield 34.2%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolventHCID 21493386Dce thfSolvent

Conditions

Temperature
70 °C

Procedure

The (S)-2-amino-3-phenyl-1-(6-(pyrimidin-5-yl)indolin-1-yl)propan-1-one (39.0 mg, 110 μmol) was dissolved in a DCE/THF mixture 1.5 mL. Thiazole-4-carbaldehyde (13 mg, 110 μmol), diisopropylethyl amine (20 μl, 110 μmol), and sodium triacetoxyborohydride (48 mg, 230 μmol) was added to the reaction mixture. The resulting solution was heated to 70° C. and stirred for three hours. LCMS indicated starting material was still present. 24 mg of sodium cyanoborohydride was added and the solution was stirred at 70° C. overnight to completion. The reaction mixture was diluted with dichloromethane and basified with saturated sodium bicarbonate. The layers were separated and the organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue was then purified on an SCX column eluting with 0 to 2M ammonia in methanol solution to give impure product. This material was then purified by medium pressure chromatography (silica gel, 0 to 6.5% 2M ammonia in methanol: dichloromethane) to give the desired product (S)-3-phenyl-1-(6-(pyrimidin-5-yl)indolin-1-yl)-2-(thiazol-4-ylmethylamino)propan-1-one (16.6 mg, 33% yield). MS ESI (pos.) m/e: 442.1 (M+H).

Workup

  1. stirringthe solution was stirred at 70° C. overnight to completion
  2. customThe layers were separated
  3. dry with materialthe organic layer was dried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was then purified on an SCX column
  6. washeluting with 0 to 2M ammonia in methanol solution
  7. customto give impure product
  8. customThis material was then purified by medium pressure chromatography (silica gel, 0 to 6.5% 2M ammonia in methanol: dichloromethane)

Sources & evidence

ORD record
ord-646e734636eb479d9c5948a09701641d
Source dataset
uspto-grants-2014_07
Patent number
US08785468B2

Reaction notes

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