4-Hydroxypyrrolidine → HCID 89689630, compound

HRID 877543Notes

Reaction equation

HRID 877543 reaction equation
[S:1]1[C:5]2[CH:6]=[C:7]([NH:10][C:11]3[N:16]=[CH:15][C:14]([C:17]4[S:18][CH:19]=[C:20]([C:22](OCC)=[O:23])[N:21]=4)=[C:13]([NH:27][CH:28]([CH3:30])[CH3:29])[CH:12]=3)[CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.[NH:31]1[CH2:35][CH2:34][CH:33]([OH:36])[CH2:32]1>CO>[S:1]1[C:5]2[CH:6]=[C:7]([NH:10][C:11]3[N:16]=[CH:15][C:14]([C:17]4[S:18][CH:19]=[C:20]([C:22]([N:31]5[CH2:35][CH2:34][CH:33]([OH:36])[CH2:32]5)=[O:23])[N:21]=4)=[C:13]([NH:27][CH:28]([CH3:29])[CH3:30])[CH:12]=3)[CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1

Participants

4

Reactant 2

HCID 982104-HydroxypyrrolidineHCID 89689564HCID 89689564, compound

Product 1

HCID 89689630HCID 89689630, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
80 °C

Procedure

The ethyl 2-(6-(benzo[d]thiazol-6-ylamino)-4-(isopropylamino)pyridin-3-yl)thiazole-4-carboxylate (Example 20) (100 mg, 0.228 mmol) was dissolved in methanol (10 mL) and to it pyrrolidin-3-ol (0.455 mmol, 2 equiv) was added and heated at 80° C. for 2 h. The reaction mixture was concentrated, the crude obtained was purified on preparative TLC to obtain (2-(6-(benzo[d]thiazol-6-ylamino)-4-(isopropylamino)pyridin-3-yl)thiazol-4-yl)(3-hydroxypyrrolidin-1-yl)methanone. 1H NMR: 400 MHz, DMSO-d6: δ 1.24 (d, J=4.00 Hz, 6H), 1.85-1.86 (m, 3H), 3.46-3.50 (m, 1H), 3.56-3.57 (m, 1H), 3.72-3.73 (m, 1H), 3.90-3.91 (m, 1H), 4.35 (bs, 1H), 5.00-5.01 (m, 1H), 6.18 (s, 1H), 7.58 (dd, J=2.00, 9.00 Hz, 1H), 7.95-7.97 (m, 1H), 8.13-8.13 (m, 1H), 8.14-8.18 (m, 1H), 8.52-8.52 (m, 1H), 8.72-8.72 (m, 1H), 9.16 (s, 1H), 9.37 (s, 1H). LC/MS: Ascentis Express C18, 5×2.1 mm-2.7 μm; Solvent A=2% ACN: 98% H2O: 10 mM NH4COOH; Solvent B=98% ACN: 2% H2O: 10 mM NH4COOH; gradient 0-100% B over 3 min; retention time: 1.883 min; LCMS (ES-API), m/z 481.2 (M+H). HPLC: Sunfire C18 (150×4.6 mm), 3.5 micron; Solvent A=5% ACN: 95% H2O: 0.05% TFA pH=2.5; Solvent B=95% ACN: 5% H2O: 0.05% TFA pH=2.5; gradient 0-100% B over 15 min (23 min run time); Flow rate: 1.0 μL/min; Retention time: 5.062 min; Purity: 92.2%.

Workup

  1. additionwas added
  2. concentrationThe reaction mixture was concentrated
  3. customthe crude obtained
  4. customwas purified on preparative TLC

Sources & evidence

ORD record
ord-822aef9c7de94d219dc8f817dc263bc0
Source dataset
uspto-grants-2015_03
Patent number
US08987311B2

Reaction notes

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