Formic Acid → HCID 59463485, compound

HRID 1712990Notes

Reaction equation

HRID 1712990 reaction equation
[CH:1]1([CH2:6][CH:7]([C:26]2[CH:31]=[CH:30][C:29]([S:32]([N:35]3[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]3)(=[O:34])=[O:33])=[CH:28][CH:27]=2)[C:8]([NH:10][C:11]2[S:12][C:13]3[C:18]([N:19]=2)=[CH:17][CH:16]=[C:15]([N:20]2[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)[N:14]=3)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH:41](O)=O>C=O>[CH:1]1([CH2:6][C@H:7]([C:26]2[CH:27]=[CH:28][C:29]([S:32]([N:35]3[CH2:36][CH2:37][N:38]([CH3:41])[CH2:39][CH2:40]3)(=[O:34])=[O:33])=[CH:30][CH:31]=2)[C:8]([NH:10][C:11]2[S:12][C:13]3[C:18]([N:19]=2)=[CH:17][CH:16]=[C:15]([N:20]2[CH2:21][CH2:22][O:23][CH2:24][CH2:25]2)[N:14]=3)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 284Formic AcidHCID 16116992HCID 16116992, compound

Product 1

HCID 59463485HCID 59463485, compound

Reagents, catalysts & solvents 1

HCID 712FormaldehydeSolvent

Conditions

Temperature
70 °C

Procedure

Title compound H, 3-Cyclopentyl-N-(5-morpholin-4-yl-thiazolo[5,4-b]pyridin-2-yl)-2-[4-(piperazine-1-sulfonyl)-phenyl]-propionamide (0.21 g, 0.354 mmol was suspended in formaldehyde (2 mL) to which 1 mL of formic acid was added. The mixture was heated to 70° C. for 7 h before being cooled and subsequently quenched into 2N NaOH and extracted with ethyl acetate. The combined organic layer was dried over MgSO4, filtered and evaporated to provide a brown foam which was purified over silica (0-20% EtOAc: methanol) to afford a white foam. This material was purified on a Chiracel column to afford pure (R)-3-Cyclopentyl-2-[4-(4-methyl-piperazine-1-sulfonyl)-phenyl]-N-(5-morpholin-4-yl-thiazolo[5,4-b]pyridin-2-yl)-propionamide as a white solid. 1H NMR (400 MHz, DMSO) δ 1.14 (m, 2H) 1.43 (d, J=4.80 Hz, 2H) 1.57 (d, J=8.34 Hz, 3H) 1.72 (d, J=5.05 Hz, 2H) 1.75-1.83 (m, 1H) 2.10 (s, 3H) 2.16 (m, 1H) 2.33 (d, J=4.04 Hz, 4H) 2.87 (s, 4H) 3.41-3.49 (m, 4H) 3.67-3.74 (m, 4H) 4.07 (t, J=7.58 Hz, 1H) 6.97 (d, J=9.09 Hz, 1H) 7.64-7.69 (m, 2H) 7.69-7.75 (m, 2H) 7.87 (d, J=8.84 Hz, 1H)

Workup

  1. additionwas added
  2. temperaturebefore being cooled
  3. customsubsequently quenched into 2N NaOH
  4. extractionextracted with ethyl acetate
  5. dry with materialThe combined organic layer was dried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customto provide a brown foam which
  9. customwas purified over silica (0-20% EtOAc: methanol)
  10. customto afford a white foam
  11. customThis material was purified on a Chiracel column

Sources & evidence

ORD record
ord-656693ec229644bdaff360ff70bb5183
Source dataset
uspto-grants-2010_09
Patent number
US07795257B2

Reaction notes

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