HCID 73425568, compound → HCID 73504574, compound

HRID 590800Notes

Reaction equation

HRID 590800 reaction equation
N1(C2C3C=NC(NC(=O)N)=CC=3NN=2)CCOCC1.[CH3:20][N:21]1[CH2:25][C@@H:24]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C@H:23]([NH:32][C:33]([NH:35][C:36]2[N:41]=[CH:40][C:39]3[C:42]([N:45]4[CH2:50][CH2:49][O:48][CH2:47][CH2:46]4)=[N:43][NH:44][C:38]=3[CH:37]=2)=[O:34])[CH2:22]1>CO>[CH3:20][N:21]1[CH2:25][C@H:24]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C@@H:23]([NH:32][C:33]([NH:35][C:36]2[N:41]=[CH:40][C:39]3[C:42]([N:45]4[CH2:50][CH2:49][O:48][CH2:47][CH2:46]4)=[N:43][NH:44][C:38]=3[CH:37]=2)=[O:34])[CH2:22]1

Participants

4

Reactant 2

HCID 73425568HCID 73425568, compoundHCID 131734496HCID 131734496, compound

Product 1

HCID 73504574HCID 73504574, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The enatiomers of 1-[(3R and S, 4S and R)-1-Methyl-4-phenylpyrrolidin-3-yl]-3-(3-morpholin-4-yl-1H-pyrazolo[4,3-c]pyridin-6-yl)urea (63.5 mg, 0.098 mmol) were separated by SFC (Berger Multigram II SFC, column: Chiral Technology IC 2.1×25 cm, 5 uM, mobile phase: 40% to 60% MeOH+0.25% dimethyl ethylamine in CO2(1), flow rate: 70 mL/min, 12 min run time). The fractions were collected and the solvent evaporated in vacuo, dissolved in ACN/water, and lyophilized to afford 1-[(3R,4S)-1-methyl-4-phenylpyrrolidin-3-yl]-3-(3-morpholin-4-yl-1H-pyrazolo[4,3-c]pyridin-6-yl)urea (15.6 mg, 0.037 mmol, 50%) and 1-[(3S,4R)-1-methyl-4-phenylpyrrolidin-3-yl]-3-(3-morpholin-4-yl-1H-pyrazolo[4,3-c]pyridin-6-yl)urea (Example 42 was obtained as the trifluoroacetic acid salt of the compound). MS ESI calc'd. For C22H27N7O2 [M+1]+ 422. found 422. 1H NMR (500 MHz, DMSO-d6) δ 12.0 (s, 1H), 8.90 (s, 1H), 8.79 (s, 1H), 7.88-7.80 (m, 1H), 7.35 (s, 1H), 7.35-7.23 (m, 4H), 7.23-7.14 (m, 1H), 4.21-4.18 (m, 1H), 3.82-3.69 (m, 4H), 3.36-3.30 (m, 4H), 3.13-3.01 (m, 2H), 2.82 (dd, J=4.5, 9.4 Hz, 1H), 2.54 (dd, J=4.5, 9.4 Hz, 1H), 2.43-2.33 (m, 1H), 2.28 (s, 3H) (Example 41). MS ESI calc'd. For C22H27N7O2 [M+1]+ 422. found 422. 1H NMR (500 MHz, DMSO-d6) δ 12.02 (s, 1H), 8.97 (s, 1H), 8.79 (s, 1H), 7.88-7.80 (m, 1H), 7.32 (s, 1H), 7.35-7.23 (m, 4H), 7.23-7.14 (m, 1H), 4.21-4.18 (m, 1H), 3.81-3.70 (m, 4H), 3.36-3.30 (m, 4H), 3.13-3.01 (m, 2H), 2.82 (dd, J=4.5, 9.4 Hz, 1H), 2.54 (dd, J=4.5, 9.4 Hz, 1H), 2.43-2.33 (m, 1H), 2.28 (s, 3H). (Example 42).

Workup

  1. customThe fractions were collected
  2. customthe solvent evaporated in vacuo
  3. dissolutiondissolved in ACN/water

Sources & evidence

ORD record
ord-ca4a4b52d8324b159f7239a0a6b40af3
Source dataset
uspto-grants-2016_01
Patent number
US09233979B2

Reaction notes

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