HCID 86705982, compound → HCID 56966072, compound

HRID 1408221Notes

Reaction equation

HRID 1408221 reaction equation
[CH2:1]([N:3]([CH2:69][CH3:70])[C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:49])[C:12]2[CH:48]=[CH:47][CH:46]=[C:14]([C:15]([N:17]([CH3:45])[CH2:18][CH2:19][N:20]([CH3:44])[CH2:21][CH2:22][O:23][CH2:24][CH2:25][O:26][CH2:27][CH2:28][O:29][CH2:30][CH2:31][NH:32][C:33](=[O:43])[NH:34]CCN3CCOCC3)=[O:16])[CH:13]=2)=[C:6]([C:50]2[CH:55]=[C:54]([C:56](=[O:68])[NH:57][C@@H:58]3[C:67]4[C:62](=[CH:63][CH:64]=[CH:65][CH:66]=4)[CH2:61][CH2:60][CH2:59]3)[CH:53]=[CH:52][N:51]=2)[CH:5]=1)[CH3:2].C(N(CC)C1C=CC(NC(C2C=C(C(=O)N(C)CCN(C)CCOCCOCCOCCNC(=O)OC3C=CC([N+]([O-])=O)=CC=3)C=CC=2)=O)=C(C2C=C(C(=O)N[C@@H]3C4C(=CC=CC=4)CCC3)C=CN=2)C=1)C>CO.CN1C(=O)CCC1>[NH2:34][C:33](=[O:43])[NH:32][CH2:31][CH2:30][O:29][CH2:28][CH2:27][O:26][CH2:25][CH2:24][O:23][CH2:22][CH2:21][N:20]([CH3:44])[CH2:19][CH2:18][N:17]([CH3:45])[C:15](=[O:16])[C:14]1[CH:46]=[CH:47][CH:48]=[C:12]([C:11]([NH:10][C:7]2[CH:8]=[CH:9][C:4]([N:3]([CH2:1][CH3:2])[CH2:69][CH3:70])=[CH:5][C:6]=2[C:50]2[CH:55]=[C:54]([C:56](=[O:68])[NH:57][C@@H:58]3[C:67]4[C:62](=[CH:63][CH:64]=[CH:65][CH:66]=4)[CH2:61][CH2:60][CH2:59]3)[CH:53]=[CH:52][N:51]=2)=[O:49])[CH:13]=1

Participants

5

Reactant 2

HCID 86705982HCID 86705982, compoundHCID 86705983HCID 86705983, compound

Product 1

HCID 56966072HCID 56966072, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

This compound was prepared according to the procedure described for the synthesis of (S)—N1-(4-(diethylamino)-2-(4-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)pyridin-2-yl)phenyl)-N3-methyl-N3-(17-methyl-1-morpholino-4-oxo-8,11,14-trioxa-3,5,17-triazanonadecan-19-yl)isophthalamide Example 223 substituting ammonia in methanol in place of 2-morpholinoethanamine. Into a 100-mL round-bottom flask, was placed a solution of (S)-4-nitrophenyl 1-(3-(4-(diethylamino)-2-(4-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)pyridin-2-yl)phenylcarbamoyl)phenyl)-2,5-dimethyl-1-oxo-8,11,14-trioxa-2,5-diazahexadecan-16-ylcarbamate (100 mg, 0.10 mmol, 1.00 equiv) in NMP (5 mL), methanol (saturated with NH3) (5 mL). The resulting solution was stirred for 3 h at room temperature. The resulting mixture was washed with 2×30 mL of water. The resulting mixture was concentrated under vacuum. The crude product (100 mg) was purified by Prep-HPLC with the following conditions (1#-PreP-HPLC-001 (SHIMADZU)): Column, SunFire Prep C18, 19*150 mm 5 um; mobile phase, water with 0.05% TFA and CH3CN (22% CH3CN up to 38% in 6 min, up to 100% in 1 min, down to 22% in 0.7 min); Detector, Waters2545 UvDector 254&220 nm. This resulted in 26 mg (21%) of (S)—N1-(1-amino-14-methyl-1-oxo-5,8,11-trioxa-2,14-diazahexadecan-16-yl)-N3-(4-(diethylamino)-2-(4-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)pyridin-2-yl)phenyl)-N1-methylisophthalamide as yellow oil. LC-MS (ES, m/z): 851 [M+H]+ H-NMR (300 MHz, CD3OD, ppm): 8.96˜8.94 (d, J=5.1 Hz, 1H), 8.71˜8.68 (m, 1H), 8.38 (s, 1H), 8.16˜8.12 (m, 2H), 7.88 (s, 1H), 7.87˜7.86 (m, 1H), 7.78˜7.73 (m, 2H), 7.58˜7.54 (m, 1H), 7.25˜7.15 (m, 4H), 5.39 (s, 1H), 3.93 (s, 5H), 3.76˜3.61 (m, 12H), 3.57˜3.48 (m, 3H), 3.27˜3.23 (m, 2H), 3.13˜3.09 (m, 5H), 2.91˜2.84 (m, 3H), 2.05˜1.91 (m, 5H), 1.31˜1.22 (m, 6H).

Workup

  1. customThis compound was prepared
  2. customInto a 100-mL round-bottom flask, was placed
  3. washThe resulting mixture was washed with 2×30 mL of water
  4. concentrationThe resulting mixture was concentrated under vacuum
  5. customThe crude product (100 mg) was purified by Prep-HPLC with the following conditions (1#-PreP-HPLC-001 (SHIMADZU))
  6. waitmobile phase, water with 0.05% TFA and CH3CN (22% CH3CN up to 38% in 6 min
  7. waitup to 100% in 1 min
  8. waitdown to 22% in 0.7 min)
  9. customThis resulted in 26 mg (21%) of (S)—N1-(1-amino-14-methyl-1-oxo-5,8,11-trioxa-2,14-diazahexadecan-16-yl)-N3-(4-(diethylamino)-2-(4-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)pyridin-2-yl)phenyl)-N1-methylisophthalamide as yellow oil

Sources & evidence

ORD record
ord-2d09a5dee8bb4dc6b360606c0be00213
Source dataset
uspto-grants-2014_12
Patent number
US08916569B2

Reaction notes

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