Triethylamine → (S)-2-((1-(2-(3-chloro-1,2-dimethyl-1H-indol-5-ylamino)pyrimidin-4-yl)-3-methyl-1H-pyrazol-4-yl)methyl)isoxazolidin-4-ol

HRID 1503354Notes

Reaction equation

HRID 1503354 reaction equation
[Cl:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([NH:11][C:12]3[N:17]=[C:16]([N:18]4[CH:22]=[C:21]([CH:23]=O)[C:20]([CH3:25])=[N:19]4)[CH:15]=[CH:14][N:13]=3)[CH:9]=2)[N:4]([CH3:26])[C:3]=1[CH3:27].Cl.[O:29]1[CH2:33][C@@H:32]([OH:34])[CH2:31][NH:30]1.C(N(CC)CC)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCl>[Cl:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([NH:11][C:12]3[N:17]=[C:16]([N:18]4[CH:22]=[C:21]([CH2:23][N:30]5[CH2:31][C@H:32]([OH:34])[CH2:33][O:29]5)[C:20]([CH3:25])=[N:19]4)[CH:15]=[CH:14][N:13]=3)[CH:9]=2)[N:4]([CH3:26])[C:3]=1[CH3:27]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 66855047(4S)-1,2-oxazolidin-4-ol hydrochlorideHCID 866989881-(2-(3-chloro-1,2-dimethyl-1H-indol-5-ylamino)pyrimidin-4-yl)-3-methyl-1H-pyrazole-4-carbaldehyde

Product 1

HCID 118022801(S)-2-((1-(2-(3-chloro-1,2-dimethyl-1H-indol-5-ylamino)pyrimidin-4-yl)-3-methyl-1H-pyrazol-4-yl)methyl)isoxazolidin-4-ol

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a slurry of Intermediate 3 (190 mg, 0.5 mmol), (S)-isoxazolidin-4-ol hydrochloride (95 mg, 0.75 mmol) and triethylamine (0.4 mL) in 10 mL of dichloromethane, was added NaBH(OAc)3 (0.32 g, 1.5 mmol) at room temperature. The reaction was stirred for 12 hour at room temperature and then quenched with 1N—NaOH. It was extracted with ethyl acetate and washed twice with brine. The collected organic layer was dried over anhydrous sodium sulfate and then concentrated in vacuo. The resulting residue was purified by silica gel chromatography (DCM/MeOH) to afford desired Compound No. 31 as a pale yellow solid (159 mg, 70%); MS (ESI) m/z 454 [M+H]+. 1H NMR (300 MHz, CDCl3) δ 8.43 (s, 1H), 8.34 (d, J=5.4 Hz, 1H), 7.89 (s, 1H), 7.68 (s, 1H), 7.14-7.16 (m, 3H), 4.73 (brs, 1H), 4.23 (brs, 1H), 3.92-3.96 (m, 2H), 3.84 (brs, 1H), 3.63 (s, 3H), 3.25 (brs, 1H), 2.73 (brs, 1H), 2.40 (s, 3H), 2.36 (s, 3H

Workup

  1. customquenched with 1N—NaOH
  2. extractionIt was extracted with ethyl acetate
  3. washwashed twice with brine
  4. dry with materialThe collected organic layer was dried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by silica gel chromatography (DCM/MeOH)

Sources & evidence

ORD record
ord-bc8171de1c364cc4a8c78487e4dc1540
Source dataset
uspto-grants-2015_12
Patent number
US09212178B2

Reaction notes

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