Phosphoric Acid → HCID 86701818, compound

HRID 338666Notes

Reaction equation

HRID 338666 reaction equation
[NH2:1][C@:2]12[CH2:43][CH2:42][C@@H:41]([C:44]([CH3:46])=[CH2:45])[C@@H:3]1[C@@H:4]1[C@@:17]([CH3:20])([CH2:18][CH2:19]2)[C@@:16]2([CH3:21])[C@@H:7]([C@:8]3([CH3:40])[C@@H:13]([CH2:14][CH2:15]2)[C:12]([CH3:23])([CH3:22])[C:11]([C:24]2[CH2:29][CH2:28][C@@H:27]([C:30]([O:32][CH2:33][C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)=[O:31])[CH2:26][CH:25]=2)=[CH:10][CH2:9]3)[CH2:6][CH2:5]1.P(=O)(O)(O)O.[K].Cl[CH2:54][CH2:55][N:56]1[CH2:61][C@@H:60]2[CH2:62][C@H:57]1[CH2:58][S:59]2(=[O:64])=[O:63].[I-].[K+]>>[O:64]=[S:59]1(=[O:63])[CH2:58][C@@H:57]2[CH2:62][C@H:60]1[CH2:61][N:56]2[CH2:55][CH2:54][NH:1][C@:2]12[CH2:43][CH2:42][C@@H:41]([C:44]([CH3:46])=[CH2:45])[C@@H:3]1[C@@H:4]1[C@@:17]([CH3:20])([CH2:18][CH2:19]2)[C@@:16]2([CH3:21])[C@@H:7]([C@:8]3([CH3:40])[C@@H:13]([CH2:14][CH2:15]2)[C:12]([CH3:23])([CH3:22])[C:11]([C:24]2[CH2:29][CH2:28][C@@H:27]([C:30]([O:32][CH2:33][C:34]4[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=4)=[O:31])[CH2:26][CH:25]=2)=[CH:10][CH2:9]3)[CH2:6][CH2:5]1

Participants

6

Reactant 5

HCID 1004Phosphoric AcidHCID 4875Potassium IodideHCID 5462222PotassiumHCID 86692345(R)-benzyl 4-((1R,3 aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3 a-amino-5 a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)cyclohex-3-enecarboxylateHCID 86701799HCID 86701799, compound

Product 1

HCID 86701818HCID 86701818, compoundYield 55.5%

Conditions

Temperature
120 °C

Procedure

In a 15 mL medium pressure flask was added (R)-benzyl 4-((1R,3 aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-amino-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)cyclohex-3-enecarboxylate (70 mg, 0.112 mmol), phosphoric acid, potassium salt (119 mg, 0.561 mmol), (1S,4S)-5-(2-chloroethyl)-2-thia-5-azabicyclo[2.2.1]heptane 2,2-dioxide (70.6 mg, 0.337 mmol) and potassium iodide (55.9 mg, 0.337 mmol). The solid mixture was dried at 50° C. vacuum oven for 15 mins and filled with N2 (g). Acetonitrile (3 mL) was added and the mixture was heated at 120° C. After 22 h, the resulting creamy reaction was cooled to rt and filtered. The light yellow paste obtained was washed with DCM (25 mL). The liquid filtrate was concentrated to give crude product as a light brown solid which was purified by reverse phase HPLC using prep-HPLC method 15 to give the title compound (67.2 mg, 0.062 mmol, 55.5% yield) as a white solid. LC/MS: m/e 797.6 (M+H)+, 4.68 min (method 8). 1H NMR (400 MHz, CHLOROFORM-d) δ 7.42-7.32 (m, 5H), 5.35 (br. s., 1H), 5.18 (d, J=4.4 Hz, 1H), 5.14 (s, 2H), 4.78 (s, 1H), 4.70 (s, 1H), 4.18 (br. s., 1H), 3.58 (br. s., 1H), 3.37 (dd, J=13.4, 2.7 Hz, 1H), 3.32-3.22 (m, 2H), 3.21-3.15 (m, 1H), 3.07 (d, J=13.0 Hz, 1H), 3.00 (dd, J=13.2, 3.2 Hz, 1H), 2.93-2.74 (m, 2H), 2.67-2.54 (m, 2H), 2.45-2.29 (m, 8H), 2.27-2.11 (m, 4H), 2.07-1.88 (m, 6H), 1.80-1.73 (m, 1H), 1.70 (s, 3H), 1.67 (br. s., 1H), 1.60-1.42 (m, 8H), 1.38 (d, J=10.8 Hz, 2H), 1.31 (br. s., 1H), 1.10 (s, 3H), 1.04 (s, 3H), 0.94 (s, 3H), 0.93 (s, 3H), 0.87 (s, 3H). 13C NMR (101 MHz, CHLOROFORM-d) δ 175.7, 148.1, 147.2, 139.3, 136.2, 128.5, 128.1, 128.0, 122.6, 121.0, 111.4, 77.2, 70.5, 66.1, 61.5, 60.7, 56.2, 53.0, 52.7, 49.3, 49.2, 48.8, 44.8, 42.1, 41.7, 40.83-40.72, 40.7, 39.0, 37.5, 36.9, 36.1, 33.8, 32.8, 31.6, 29.6, 28.3, 27.7 (br. s., 1C), 27.70-27.57, 25.9, 25.8, 25.2, 21.5, 20.9, 19.6, 19.4, 16.4, 16.1, 14.5.

Workup

  1. customThe solid mixture was dried at 50° C. vacuum oven for 15 mins
  2. additionfilled with N2 (g)
  3. additionAcetonitrile (3 mL) was added
  4. customthe resulting creamy reaction
  5. temperaturewas cooled to rt
  6. filtrationfiltered
  7. customThe light yellow paste obtained
  8. washwas washed with DCM (25 mL)
  9. concentrationThe liquid filtrate was concentrated
  10. customto give crude product as a light brown solid which
  11. customwas purified by reverse phase

Sources & evidence

ORD record
ord-45eda3f8a6b84800ba94a845b018a76a
Source dataset
uspto-grants-2014_11
Patent number
US08889854B2

Reaction notes

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