Acetic Acid → N-(8-oxo-4-oxa-1,7-diazatricyclo[9.6.1.012,17]octadeca-11(18),12,14,16-tetraen-9(S)-yl)-3(R)-[3-[4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinamic acid

HRID 382170Notes

Reaction equation

HRID 382170 reaction equation
C([O:8][C:9](=[O:51])[CH2:10][C@@H:11]([N:34]1[CH:38]=[CH:37][C:36]([C:39]2[CH:44]=[CH:43][C:42]([C:45]3[CH:50]=[CH:49][N:48]=[CH:47][CH:46]=3)=[CH:41][CH:40]=2)=[CH:35]1)[C:12]([NH:14][C@H:15]1[CH2:31][C:30]2=[CH:32][N:23]([C:24]3[C:29]2=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH2:22][CH2:21][O:20][CH2:19][CH2:18][NH:17][C:16]1=[O:33])=[O:13])C1C=CC=CC=1.C(O)=O.CC(O)=O>CCOC(C)=O.CCO.C1COCC1.[Pd]>[O:33]=[C:16]1[C@@H:15]([NH:14][C:12](=[O:13])[C@H:11]([N:34]2[CH:38]=[CH:37][C:36]([C:39]3[CH:44]=[CH:43][C:42]([C:45]4[CH:46]=[CH:47][N:48]=[CH:49][CH:50]=4)=[CH:41][CH:40]=3)=[CH:35]2)[CH2:10][C:9]([OH:51])=[O:8])[CH2:31][C:30]2=[CH:32][N:23]([C:24]3[C:29]2=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH2:22][CH2:21][O:20][CH2:19][CH2:18][NH:17]1

Participants

6

Reactant 3

HCID 176Acetic Acid2×HCID 284Formic Acid2×HCID 15459682N-(8-oxo-4-oxa-1,7-diazatricyclo[9.6.1.012,17]octadeca-11(18),12,14,1 6-tetraen-9(S)-yl)-3(R)-[3-[4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinamic acid benzyl ester

Product 1

HCID 15459681N-(8-oxo-4-oxa-1,7-diazatricyclo[9.6.1.012,17]octadeca-11(18),12,14,16-tetraen-9(S)-yl)-3(R)-[3-[4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinamic acidYield 46%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalyst3×HCID 18365940Tetrahydrofuran ethyl acetate ethanolSolvent

Procedure

To a solution of N-(8-oxo-4-oxa-1,7-diazatricyclo[9.6.1.012,17]octadeca-11(18),12,14,1 6-tetraen-9(S)-yl)-3(R)-[3-[4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinamic acid benzyl ester (185 mg, 0.280 mmol) in EtOAc/EtOH/THF was added in succession 10% palladium on carbon (50 mg) and 88% formic acid (0.1 mL). After 1.5 hours, HOAc (1 mL) was added. After 16 hours, more 10% palladium on carbon (25 mg), 88% formic acid (0.1 mL), and HOAc (1 mL) was added. At 24 hours, more 10% palladium on carbon (25 mg) was added. After 25 hours total elapsed time, the catalyst was filtered off. The filtrate was concentrated to a crude solid. The product dissolved in a minimal amount of MeOH/EtOAc, and inorganic particulates were filtered away. The filtrate was concentrated to a solid that was triturated with CH2Cl2/hex to give 76 mg (46%) of N-(8-oxo-4-oxa-1,7-diazatricyclo[9.6.1.012,17]octadeca-11(18),12,14,16-tetraen-9(S)-yl)-3(R)-[3-[4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinamic acid as a yellow solid, mp >172° C. (d).

Workup

  1. waitAfter 16 hours
  2. waitAt 24 hours
  3. waitAfter 25 hours total elapsed time
  4. filtrationthe catalyst was filtered off
  5. concentrationThe filtrate was concentrated to a crude solid
  6. dissolutionThe product dissolved in a minimal amount of MeOH/EtOAc, and inorganic particulates
  7. filtrationwere filtered away
  8. concentrationThe filtrate was concentrated to a solid
  9. customthat was triturated with CH2Cl2/hex

Sources & evidence

ORD record
ord-130c8fc1930c4fccb2cda8f957ff8b4f
Source dataset
uspto-grants-2001_10
Patent number
US06306892B1

Reaction notes

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