Triethylamine → 1-((4-methyl-1-(2-(1-methyl-1H-indazol-5-ylamino)pyrimidin-4-yl)-1H-pyrrol-3-yl)methyl)azetidin-3-ol

HRID 539903Notes

Reaction equation

HRID 539903 reaction equation
[CH3:1][C:2]1[C:3]([CH:24]=O)=[CH:4][N:5]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]3[CH:15]=[C:16]4[C:20](=[CH:21][CH:22]=3)[N:19]([CH3:23])[N:18]=[CH:17]4)[N:8]=2)[CH:6]=1.Cl.[NH:27]1[CH2:30][CH:29]([OH:31])[CH2:28]1.C(N(CC)CC)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCl>[CH3:1][C:2]1[C:3]([CH2:24][N:27]2[CH2:30][CH:29]([OH:31])[CH2:28]2)=[CH:4][N:5]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]3[CH:15]=[C:16]4[C:20](=[CH:21][CH:22]=3)[N:19]([CH3:23])[N:18]=[CH:17]4)[N:8]=2)[CH:6]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 27592903-Hydroxyazetidine hydrochlorideHCID 5049666Sodium triacetoxyborohydrideHCID 866989924-methyl-1-(2-(1-methyl-1H-indazol-5-ylamino)pyrimidin-4-yl)-1H-pyrrole-3-carbaldehyde

Product 1

HCID 866989941-((4-methyl-1-(2-(1-methyl-1H-indazol-5-ylamino)pyrimidin-4-yl)-1H-pyrrol-3-yl)methyl)azetidin-3-ol

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a slurry of intermediate 13 (0.45 g, 1.3 mmol), 3-azetidinol hydrochloride (0.3 g, 2.7 mmol) and triethylamine (0.76 mL) in 50 mL of dichloromethane, was added NaBH(OAc)3 (0.86 g, 4.5 mmol) at room temperature. The reaction was stirred for 12 hour at room temperature and then quenched with 1N—NaOH. It was extracted with dichloromethane (×2) and washed with brine. The collected organic layers were dried over anhydrous sodium sulfate and then concentrated in vacuo. The resulting residue was purified by column chromatography to afford desired Compound No. 143 as a pale yellow solid (0.27 g, 51%); MS (ESI) m/z 391 [M+H]+.]+; 1H NMR (300 MHz, DMSO-d6) δ 9.75 (s, 1H), 8.48 (d, 1H, J=5.4 Hz), 8.30 (s, 1H), 8.21 (s, 1H), 7.99 (s, 1H), 7.62 (m, 2H), 7.12 (d, 1H, J=5.4 Hz), 5.34 (m, 1H), 4.19 (m, 1H), 4.04 (s, 3H), 3.49 (m, 2H), 3044 (s, 2H), 2.77 (m, 2H), 2.29 (m, 3H).

Workup

  1. customquenched with 1N—NaOH
  2. extractionIt was extracted with dichloromethane (×2)
  3. washwashed with brine
  4. dry with materialThe collected organic layers were dried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by column chromatography

Sources & evidence

ORD record
ord-f151782efeec41cea1987a6a0a475799
Source dataset
uspto-grants-2014_10
Patent number
US08871778B2

Reaction notes

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